Relationship between arteriosclerosis obliterans and the ratio of serum eicosapentaenoic acid to arachidonic acid.

PURPOSE: A low ratio of serum eicosapentaenoic acid to arachidonic acid (EPA/AA) has been associated with coronary artery disease. We retrospectively examined serum concentrations of polyunsaturated fatty acids in patients with arteriosclerosis obliterans (ASO) and in non-atherosclerotic patients. METHODS: From April 2011 to March 2012, serum EPA/AA was retrospectively examined in 33 consecutive outpatients with ASO complicated by intermittent claudication and 21 outpatients with hypercholesterolemia without ASO as controls. The Student's t-test was used for continuous variables and Chi-square test for categorical variables, with analysis of covariance adjusting for age, sex, body mass index, smoking, alcohol, and diabetes. RESULTS: The ASO group were significantly different with regard to mean age (71.5 vs. 63.9 year-old, p = 0.03), body mass index (21.3 vs. 24.1 kg/m(2), p = 0.002) and morbidity of diabetes mellitus (51.5 vs. 4.8%, p = 0.0004). Serum EPA/AA was significantly decreased in ASO (0.36 vs. 0.61, p = 0.03), when adjusted for age, sex, body mass index, smoking status and alcohol drinking, but was not statistically significant when adjusted for diabetes. CONCLUSION: Patients with ASO were more likely to have a low EPA/AA ratio and non- diabetic patients with ASO had a significantly reduced EPA/AA.

Metabolic syndrome among pre- and post-menopausal rural women in Bangladesh: result from a population-based study.

BACKGROUND: Prevalence of non-communicable diseases are a challenging problems among menopausal women specially in a least developed country like Bangladesh, where majority of women suffering from at least one chronic diseases after menopausal age. So, the main objective of this study was to determine the prevalence of metabolic syndrome and related risk factors in Bangladeshi pre- and post-menopausal women living in the rural setting. METHODS: This study is based on a community based cross-sectional survey among 1802 rural women aged ≥15 years. Metabolic syndrome was defined according to the criteria of NCEP-ATP III. Logistic regression was used to estimate the association between menopausal status and metabolic syndrome and its components. RESULTS: Metabolic syndrome was presented in 25.6% respondents and it was more prevalent among post-menopausal (39.3%) as compared to pre-menopausal (16.8%) women. Logistic regression analysis reveals that prevalence of metabolic syndrome was 1.78 times higher in post-menopausal women than pre-menopausal women (P = 0.001). Prevalence of high blood pressure, elevated fasting blood glucose, and high triglyceride were significantly higher in post-menopausal women than pre-menopausal women (P < 0.05). However, prevalence of low high-density lipoprotein cholesterol was significantly lower in post-menopausal women than pre-menopausal women (P < 0.001). CONCLUSIONS: Metabolic syndrome seems to be a major health problem among post-menopausal women in many developing countries like Bangladesh and proper policy emphasis should be given on its prevention and control.

Disruption of components of vascular endothelial growth factor angiogenic signalling system in metabolic syndrome. Findings from a study conducted in rural Bangladeshi women.

Metabolic syndrome (MetS) is associated with impaired angiogenesis, a process that is chiefly regulated by vascular endothelial growth factor (VEGF) upon binding to its specific receptors, VEGF-R1 and VEGF-R2. The purpose of the present study was to assess trends or patterns in plasma levels of VEGF and its soluble receptors in subjects with (MetS) or without (non-MetS) MetS; and further examine their association with clinical or metabolic parameters using a subpopulation of South Asian country. A total of 1,802 rural Bangladeshi women aged ≥15 years were studied using a population-based cross-sectional survey. Plasma levels of VEGF were found to be significantly increased (MetS vs. non-MetS: 483.9 vs. 386.9, p<0.001), whereas, the soluble forms of VEGF receptors, sVEGF-R1 and sVEGF-R2, were significantly decreased in subjects with Mets (sVEGF-R1, MetS vs. non-MetS: 512.5 vs. 631.3, p<0.001; sVEGF-R2, MetS vs. non-MetS: 9,302.8 vs. 9,787.4, p=0.004). After adjustment for age and all potential variables, multiple regression analysis revealed that plasma levels of VEGF had significant positive association with blood glucose (p = 0.019) and body mass index (p = 0.007). We also found that mean plasma levels of VEGF increased in direct proportion to levels of MetS components. The present study is the first ever to demonstrate a positive association between trends in levels of plasma VEGF and MetS using a large sample size from South Asia. The association between plasma VEGF and MetS needs further investigations in order to clearly decipher the clinical predictive value and accuracy of plasma VEGF in MetS.

Gastric injury caused by low-dose aspirin therapy in consecutive Japanese patients: a prospective study.

PURPOSE: Low-dose aspirin (<325 mg/day), administered to those with several conditions involving ischemic disorders, can cause upper gastrointestinal (GI) complications. In this prospective study, we aimed to clarify the incidence of aspirin-induced gastric ulcers in consecutive Japanese patients and identify suitable preventive measures. METHODS: We recruited 125 consecutive adult outpatients who received low-dose aspirin (enteric-coated tablets 100 mg) for >8 weeks. Endoscopy and blood tests were used to evaluate their gastric injury (which was scored using a modified Lanza scale) and anti-Helicobacter pylori antibody titer, respectively. RESULTS: We found that 39.8% of patients received either no upper GI drug or only mucoprotective drugs, 39.8% received medium-dose histamine H2 blockers, and 20.4% received proton-pump inhibitors (PPIs). Anti-H. pylori antibody titers were positive in 43.7% of patients. The incidence of definitive gastric ulcers in this population was 0.97%. Ordered logistic regression analysis revealed that the odds ratio for the increase in the modified Lanza score was 0.20 for medium-dose histamine H2 blockers and 0.09 for PPIs. CONCLUSION: The incidence of postoperative definitive gastric ulcers in Japanese patients receiving ≤100 mg enteric-coated aspirin was 0.97%. The use of PPIs and histamine H(2) blockers may prevent aspirin-induced gastric injury in such patients.

Prevalence of metabolic syndrome among rural Bangladeshi women.

We assessed prevalence of metabolic syndrome (MS) in rural women of Bangladesh using 1485 women aged ≥15 years. The prevalence rate of MS was 31.25% (NCEP ATP III modified). And 85.05% population had low HDL values. These findings are important in the development of future health prevention strategies in Bangladesh.

Evaluation of pharmacogenetic algorithm for warfarin dose requirements in Japanese patients.

BACKGROUND: Warfarin dosing is difficult to establish because of considerable interindividual variation. Thus, warfarin pharmacogenetics have attracted particular interest in relation to appropriate control of anticoagulation. METHODS AND RESULTS: The 200 eligible subjects were chosen from participants in a hospital cohort. Performance of a pharmacogenetic algorithm recently developed by the International Warfarin Pharmacogenetics Consortium (IWPC) was tested and compared with a clinical algorithm (without genotype data) by calculating the percentage of patients for whom the predicted dose deviated by less than 7 mg/week (1 mg/day) from the actual dose. The pharmacogenetic algorithm accurately identified a significantly (P<0.05) larger proportion of patients to achieve the target international normalized ratio than did the clinical algorithm (68% vs 36% for a low-dose group; and 21% vs 0% for a high-dose group). Also, an increase in warfarin dosage was found to be appropriate for the current status of alcohol drinking (4 mg/week, as against non-drinking) and smoking (3.3 mg/week, as against non-smoking). CONCLUSIONS: The IWPC pharmacogenetic algorithm has clinical application, particularly in identifying Japanese patients who require a low dosage of warfarin and are at greater risk of excessive anticoagulation.

Response of a thymic mucoepidermoid carcinoma to combination chemotherapy with cisplatin and irinotecan: a case report.

A chemotherapeutic regimen for advanced thymic carcinoma has not yet been established. We describe a patient with advanced thymic mucoepidermoid carcinoma who achieved a complete response to combination chemotherapy with cisplatin (Randa) and irinotecan hydrochloride (Campto). A 74-year-old man was admitted to our hospital because of chest pain, general fatigue, appetite loss and weight loss. Chest computed tomography examinations revealed an anterior mediastinal tumour (5.5cmx3.5cmx9.5cm) that had invaded the subcutis through the sternum. The patient was treated with three courses of cisplatin and irinotecan hydrochloride followed by radiotherapy; he has since exhibited a complete response for 3 months.

Mycotic aneurysm of the right coronary artery.

Mycotic embolism in patients with infective endocarditis is not uncommon, however, mycotic aneurysm of a coronary artery is very rare. We report the case of a 62-year-old woman with mitral valve endocarditis complicated by mycotic aneurysm of the right coronary artery. Mitral valve replacement and resection of the mycotic aneurysm with coronary artery bypass were performed.

Different contributions of polymorphisms in VKORC1 and CYP2C9 to intra- and inter-population differences in maintenance dose of warfarin in Japanese, Caucasians and African-Americans.

OBJECTIVE: To investigate pharmacokinetic and pharmacodynamic factors associated with population differences in warfarin doses needed to achieve anticoagulation, in particular the possible involvement of genetic variability in vitamin K epoxide reductase (VKOR) and CYP2C9. METHODS: Warfarin maintenance dose, unbound plasma S-warfarin concentration [Cu(S)] and INR were determined in 157 Caucasians, 172 Japanese, and 36 African-Americans stably anticoagulated patients. In a subset (n = 166), fully carboxylated plasma normal prothrombin levels (NPT) were also measured. Genotyping for seven CYP2C9 (CYP2C9*1 through 6 and *11) and seven VKORC1 variants were performed in 115 Caucasians and 64 Japanese patients and 66 healthy African-Americans. Multivariate analysis was performed to identify covariates associated with warfarin requirement. RESULTS: The relationship between NPT and Cu(S) indicated Japanese are more susceptible to inhibition of NPT production by S-warfarin than the other two populations. VKORC1 1173 C > T had a greater frequency in Japanese (89.1%) than Caucasians (42.2%) and African-Americans (8.6%). CYP2C9 variants with reduced metabolizing ability were less frequent in Japanese compared to the other two populations. The median warfarin dose was significantly higher in Caucasians than Japanese patients (5.5 versus 3.5 mg/day), however, when matched for CYP2C9*1 homozygosity, no difference in dose was observed between VKORC1 genotype-matched groups. Furthermore, VKORC1 1173C > T and CYP2C9 (*2/*3/*11) genotypes, age and weight were identified as independent covariates contributing to interpatient variability in warfarin dosage. CONCLUSIONS: Both VKORC1 and CYP2C9 polymorphisms contribute to inter-population difference in warfarin doses among the three populations, but their contribution to intra-population variability may differ within each population.

Nonocclusive mesenteric ischemia after cardiopulmonary bypass.

Nonocclusive mesenteric ischemia (NOMI) is a rare abdominal pathology caused by mucosal hypoperfusion without actual obstruction to the mesenteric arteries. We present a case of NOMI after a cardiopulmonary bypass operation. The patient was a 79-year-old woman with a history of hypertension and diabetes mellitus. A coronary bypass operation was performed with stable hemodynamic conditions, and continuous venovenous hemodialysis was performed on the second postoperative day because of renal insufficiency. After 24 h of hemodialysis, the hematocrit level increased from 29.1% to 36.1%. The patient had some vague abdominal pain on the third postoperative day with abnormal laboratory values: leukocytes 17.10 x 10(3)/microl, creatine kinase 1085 U/l, glutamic-oxyloacetic transaminase 6188 U/l, and lactate dehydrogenase 8695 U/l. Selective angiography showed diffuse stenosis of the superior mesenteric artery (SMA) without any occlusive findings on the major branches; the patient was therefore diagnosed with NOMI. An infusion of urokinase and prostaglandin E1 was started; however, disseminated intravascular coagulopathy had developed and the patient died on the 21st postoperative day as a result of multiple organ failure. The autopsy demonstrated extensive necrosis and hemorrhage in the small intestine without any occlusive findings on the major branches of the SMA.

5'-Flanking region polymorphisms of CYP2C9 and their relationship to S-warfarin metabolism in white and Japanese patients.

White and Japanese patients require different warfarin dosages to achieve therapeutic anticoagulation, but this can be only partly explained by genetic variability in the coding region of CYP2C9-a critical enzyme in the drug's metabolism. Accordingly, analysis of the -2.1-kb 5'-flanking region of CYP2C9 was undertaken in 22 white and 38 Japanese patients whose unbound oral clearance of S-warfarin had been previously determined. Thirteen single nucleotide polymorphisms (SNPs) were identified, some of which were in linkage disequilibrium with functionally defective coding region variants. Those 5'-flanking patterns linked with at least one CYP2C9*3 allele or CYP2C9*2/*3 were associated with reduced CYP2C9 activity and warfarin dose. Japanese patients possessing the wild-type promoter and coding sequences had significantly (P <.01) greater CYP2C9 activity than white patients with the corresponding genotype. In conclusion, either unidentified polymorphisms further upstream in the promoter region or environmental factor(s) account for the differences in the warfarin doses between whites and Japanese.

Population differences in S-warfarin metabolism between CYP2C9 genotype-matched Caucasian and Japanese patients.

OBJECTIVE: Our objective was to investigate population differences in the metabolic activity of cytochrome P450 (CYP) 2C9 between genotypically matched Caucasian and Japanese patients by using the unbound oral clearance of S-warfarin as an in vivo phenotypic trait measure. METHODS: Ninety Japanese and 47 Caucasian patients receiving maintenance warfarin therapy were studied. Steady-state plasma unbound concentrations of S-warfarin were measured by a chiral HPLC method coupled with an ultrafiltration technique, and unbound oral clearance for S-warfarin was estimated. By combining plasma unbound concentrations of S-warfarin with the urinary excretion rates of S-7-hydroxywarfarin, the formation clearance of S-7-hydroxywarfarin was also determined. Genotyping of CYP2C9 was performed for 6 distinct alleles (CYP2C9*1, CYP2C9*2, CYP2C9*3, CYP2C9*4, CYP2C9*5, and a T/C transition in intron 2). RESULTS: The frequency distribution of unbound oral clearance for S-warfarin obtained from Japanese patients was shifted toward higher values as compared with that in Caucasian patients. Japanese patients had lower allelic frequencies for the 5 variants than Caucasian patients. When interpopulation comparisons of CYP2C9 activity were made for genotype-matched subjects, Japanese patients with the homozygous CYP2C9*1 (wild-type) genotype (n = 85) had significantly (P <.01) greater median values for unbound oral clearance and formation clearance than Caucasian patients with the corresponding genotype (n = 26), 10.4 mL x min(-1) x kg(-1) versus 4.25 mL x min(-1) x kg(-1) and 0.015 mL x min(-1) x kg(-1) versus 0.010 mL x min(-1) x kg(-1), respectively. In addition, Japanese patients heterozygous for the CYP2C9*3 genotype (n = 4) showed a significantly (P <.05) reduced unbound oral clearance for S-warfarin, by 63%, as compared with Japanese patients possessing the homozygous CYP2C9*1 genotype. By contrast, in Caucasian patients, no significant differences were observed in this parameter between CYP2C9(*)1 homozygous subjects and those with heterozygous CYP2C9(*)2 or CYP2C9(*)3 genotypes. CONCLUSIONS: These findings indicate that population differences in the frequencies of known variant CYP2C9 alleles account only in part for the variability observed in in vivo CYP2C9 activity in different populations. In addition, a gene-dose effect of defective CYP2C9 alleles on the in vivo CYP2C9 activity is evident in Japanese patients but not in Caucasian patients. Further studies are required to identify currently unknown factor(s) (eg, transcriptional regulation) responsible for the large intrapopulation and interpopulation variability in CYP2C9 activity.

A survival case of acute mitral regurgitation and cardiogenic shock caused by subtotal occlusion of the first diagonal branch.

An 80-year-old woman was admitted with cardiogenic shock; she arrived in a deep coma with systolic blood pressure of 44 mmHg. An electrocardiogram showed ST elevation in I, aVL, V5 and V6, suggesting myocardial infarction in the lateral area of the left ventricle. A chest roentgenogram showed right pulmonary edema without cardiomegaly. Transthoracic and transesophageal echocardiograms revealed severe mitral regurgitation and a flailing anterior mitral valve leaflet, suggesting a ruptured papillary muscle. The patient was initially treated with high-dose dopamine, dobutamine and norepinephrine. Intraaortic balloon pumping was initiated after the patient's condition stabilized. She underwent emergency mitral valve replacement with a prosthetic valve. Complete rupture of the anterior papillary muscle was confirmed. Histological examination revealed necrosis of the anterior papillary muscle with inflammatory changes. She recovered uneventfully. Postoperative coronary angiography demonstrated subtotal occlusion of the first diagonal branch, and left ventriculography demonstrated akinesis of the lateral segment. This was a rare case in which subtotal occlusion of the first diagonal branch caused rupture of an anterior papillary muscle leading to severe mitral regurgitation.