Combination Therapy of Metformin and Statin May Decrease Hepatocellular Carcinoma Among Diabetic Patients in Asia

Previous studies have shown that metformin or statins may decrease hepatocellular carcinoma (HCC) in diabetic patients. Accordingly, this article evaluates whether combination therapy may further reduce HCC.Newly diagnosed type 2 diabetes mellitus (DM) patients, excluding those with history of malignancy prior to the date of DM diagnosis, were recruited to a DM cohort. DM patients developed HCC as the cancer cohort and the date for HCC diagnosis as index date. Non-cancer cohort was frequency matched with 4:1 according to age, sex, DM-year, and index date as case group from DM cohort.Patients who were treated with statins showed a 63% decreased risk of HCC (odds ratio [OR] = 0.37; 95% confidence interval [CI] = 0.27–0.49). Patients who consumed simvastatin, atorvastatin, or rosuvastatin significantly decreased risk for HCC (OR = 0.32, 0.31, and 0.22; 95% CI = 0.18–0.58, 0.19–0.52, and 0.08–0.61, respectively). Metformin combinations with simvastatin, atorvastatin, or rosuvastatin may decrease HCC (OR = 0.30, 0.30, and 0.24; 95% CI = 0.15–0.59, 0.16–0.54, and 0.08–0.70, respectively). The comorbidities for HCC were decreased by consuming simvastatin and atorvastatin (OR = 0.31 and 0.29; 95% CI = 0.14–0.67 and 0.15–0.57, respectively). Only combination therapy of metformin and simvastatin may significantly decreased HCC comorbidities (OR = 0.26; 95% CI = 0.11–0.60) in our study.In Asia, not all metformin combinations with statins may reduce the incidence of HCC and not all of this kind of combination therapy may decrease the HCC comorbidities.     

Effects of Ding-Chuan-Tang on Bronchoconstriction and Airway Leucocyte Infiltration in Sensitized Guinea Pigs

Ding-Chuan-Tang (DCT), a traditional Chinese medicine, has been used in treatment of the bronchial asthma for several centuries. However, the therapeutic mechanism of these Chinese medicine are still far from clear. To understand the mechanism of antiasthmatic property of DCT. A guinea pig model of allergic asthma was used to investigate the effects of DCT on ovalbumin-induced early and late asthmatic responses and airway inflammation, particularly the extent of eosinophil infiltration, and examine it direct β2-adrenoceptor agonist activity in guinea-pig isolated trachea. We had used three different protocals in ovalbumin sensitized guinea pigs by administrating 10 g/kg of DCT extracts to sensitized guinea pigs 30 min before antigen challenge (group I), 5 hr after antigen challenge (group II) and 2.5 g/kg once daily from the day of sensitization to the day of challenge. Our result showed that administration of DCT singificantly inhibited the antigen induced immediate asthmatic responses (IAR) in group I and inhibited both IRA and late asthmatic responses (LAR) in actively sensitized guinea pig in group III. DCT caused concentration-dependent relaxations in strips of guinea pig trachea contracted with carbachol, however ICI-118551, a selective β2-adrenoceptor antagonist, didn't significantly competitively inhibit the relaxations caused by DCT. Furthermore, examination of bronchoalveolar lavage fluid (BALF) revealed that DCT significantly inhibited the increase in percent of eosinophils in the airway after antigen challenge in three group. Histopathologic examination showed DCT suppressed the eosinophil infiltration into lung tissue. These results suggest that the antiasthmatic effect of DCT is mainly due to its bronchodilatation effect and its ability to inhibit the eosinophil into the airway and there is prophylactic effect of DCT on allergen-induced airway inflammation.     

Comparative analysis of urinary N7-(2-hydroxyethyl)guanine for ethylene oxide- and non-exposed workers

Ethylene oxide (EO), a direct alkylating agent and a carcinogen, can attack the nucleophilic sites of DNA bases to form a variety of DNA adducts. The most abundant adduct, N7-(2-hydroxyethyl)guanine (N7-HEG), can be depurinated spontaneously or enzymatically from DNA backbone to form abasic sites. Molecular dosimetry of the excised N7-HEG in urine can serve as an EO exposure and potential risk-associated biomarker. This study was to analyze N7-HEG in urine collected from 89 EO-exposed and 48 nonexposed hospital workers and 20 exposed and 10 nonexposed factory workers by using our newly developed on-line solid-phase extraction isotope-dilution LC-MS/MS method. Statistical analysis of data shows that the exposed factory workers excreted significantly greater concentrations of N7-HEG than both the nonexposed factory workers and hospital workers. Multiple linear regression analysis reveals that the EO-exposed factory workers had a significantly greater post-shift urinary N7-HEG than their nonexposed coworkers and hospital workers. These results demonstrate that analysis of urinary N7-HEG can serve as a biomarker of EO exposure for future molecular epidemiology studies to better understand the role of the EO-induced DNA adduct formation in EO carcinogenicity and certainly for routine surveillance of occupational EO exposure for the study of potential health impacts on workers.     

Chrysophanol-induced necrotic-like cell death through an impaired mitochondrial ATP synthesis in Hep3B human liver cancer cells

Liver cancer is the most common form of cancer in Taiwan and it usually responds to chemotherapy. However, patients often have side effects to the chemotherapeutic drugs. Thus new agents are urgently required to treat liver cancer. Chrysophanol, one of the anthraquinone derivatives, was reported to inhibit some human cancer cell growth which may be due to the induction of apoptosis similar to other anthraquinone derivatives though such actions have not been reported. In the present study, we reported that chrysophanol inhibits cell growth in Hep3B liver cancer cells based on the following observations: 1) induc cell morphological changes; 2) decreased percentage of viable cells; 3) induced S phase arrest of cell cycle progression; 4) induced DNA damage as measured by comet assay and DAPI staining. Chrysophanol-induced cell death however, seems to be related to necrotic processes rather than typical apoptosis. Chrysophanol induced reactive oxygen species and Ca(2+) production and decreased mitochondrial membrane potential (ΔΨm) and ATP levels in Hep3B cells. No effects were observed on known protein regulators of apoptosis such as Bax and Bcl-2. Chrysophanol-induced cell death took place independently of caspase-8 and -9. Based on our findings, we propose that chrysophanol reduces cellular ATP levels causing a drop in energy resulting in necrotic-like cell death.     

直肠癌并嗜酸性粒细胞增多1例

目的:探讨直肠癌合并嗜酸性粒细胞增多的临床特点及意义.方法:结合我院收治的1例直肠癌合并嗜酸性粒细胞增多的临床资料及国外文献报道进行综合分析.结果:直肠癌合并嗜酸性粒细胞增多患者男性表现为大便不畅伴黏液脓血样便, 血嗜酸性粒细胞增多, 比例最高达55.1%, 绝对值2.41×109/L, 结肠镜提示, 距肛门10-13 cm处可见肿物, 肠腔狭窄, 结肠镜不能通过, 组织活检病理报告, 直肠腺癌.结论:直肠癌等恶性肿瘤通过分泌嗜酸细胞克隆刺激因子引发嗜酸细胞增多.     

Lamotrigine-associated reversible severe hepatitis: A case report

Introduction

Anticonvulsant hypersensitivity syndrome is a severe idiosyncratic reaction to antiepileptic drugs. We report a case of a woman with lamotrigine-associated hepatitis who recovered spontaneously with supportive treatment.

Case Report

A 43-year-old woman was being treated with oxcarbazepine for depression and was started on lamotrigine 2 weeks prior to her presentation. The patient then developed nausea and a generalized pruritic macular rash, and was found to have elevated liver enzymes, which peaked at AST, 6079 IU/L; ALT, 6900 IU/L; total bilirubin, 3.9 mg/dL(66.7 μmol/L); alkaline phosphatase, 149 IU/L; international normalized ration (INR), 1.9. The patient showed no signs of encephalopathy and her clinical examination was essentially normal except for very mild jaundice and a diffuse erythematous pruritic macular rash. The patient was hydrated and managed with supportive care. On the third day of hospitalization, her liver enzymes had improved substantially and she was discharged. At follow-up 1 month later the patient’s liver enzymes were within the normal range.

Discussion

We hypothesize that lamotrigine was directly responsible for the patient’s rash and liver impairment given the time sequence of drug introduction and resolution of symptoms and liver enzyme abnormality once the drug was withdrawn. The patient suffered severe transaminitis when lamotrigine was added to oxcarbazepine, which resolved after termination of the medication and supportive management. We recommend monitoring the hepatic function in patients who have just been initiated on lamotrigine, especially if they develop jaundice.     

An observational,prospective study comparing tibial and humeral intraosseous access using the EZ-IO

Introduction

Intraosseous (IO) access is an alternative to conventional intravenous access. The proximal tibia and proximal humerus have been proposed as suitable sites for IO access.

Methods

A nonrandomized, prospective, observational study comparing flow rates and insertion success with tibial and humeral IO access in adults using the EZ-IO–powered drill device was conducted. The tibia was the first site of insertion, and a second IO was inserted in the humerus if clinically indicated for the same patient.

Results

Twenty-four patients were recruited, with 24 tibial and 11 humeral insertions. All EZ-IO insertions were successful at the first attempt except for 1 tibial insertion that was successful on the second attempt. All insertions were achieved within 20 seconds. Mean ease of IO insertion score (1 = easiest to 10 = most difficult) was 1.1 for both sites. We found tibial flow rates to be significantly faster using a pressure bag (165 mL/min) compared with those achieved without a pressure bag (73 mL/min), with a difference of 92 mL/min (95% confidence interval [CI]: 52, 132). Similarly, humeral flow rates were significantly faster using a pressure bag (153 mL/min) compared with humeral those achieved without pressure bag (84 mL/min), with a difference of 69 mL/min (95% CI: 39, 99). Comparing matched pairs (same patient), there was no significant difference in flow rates between tibial and humeral sites, with or without pressure bag infusion.

Conclusions

Both sites had high-insertion success rates. Flow rates were significantly faster with a pressure bag infusion than without. However, we did not find any significant difference in tibial or humeral flow rates.     

Thyrotoxic heart disease

Patients with tachyarrythmias as a result of thyroid storm have been typically treated with beta-blockers to decrease the heart rate and alleviate beta-receptor mediated symptoms such as anxiety and tremulousness. We report an unusual case of a previously well young man presenting to the emergency department with atrial flutter and who was clinically hyperthyroid. The patient was treated with propanolol to control his heart rate but suffered cardiovascular collapse. Although the patient was successfully resuscitated, he required inotropic support and intra-aortic balloon pump. The use of propanolol should be carefully considered in patients with thyrotoxic cardiomyopathy especially in those with heart failure because of the risk of exacerbation.     

Phenelzine-Induced Myocardial Injury: a Case Report

Introduction

Phenelzine is an irreversible monoamine oxidase inhibitor (MAOI). Hypertensive reactions after ingestion of tyramine-rich foods such as cheese are well known. However, a review of the available medical literature found no previous reports of myocardial infarction resulting from the ingestion of cheese by a patient taking a MAOI.

Case Report

A 34-year-old female taking phenelzine for depression developed severe chest pain 1 h after eating cheese. She was hypertensive and the electrocardiography showed ischemic changes in the antero-lateral chest leads. The chest pain and elevated blood pressure were relieved with intravenous morphine and nitroprusside. The initial serum troponin I level was normal, but serial repeat levels showed a rising trend with a peak at 4.89 ug/L (reference range <0.05 ug/L) 6 h after the initial blood draw, suggestive of a non-ST elevation myocardial infarction. The patient subsequently developed hypotension 4 h after another therapeutic dose of phenelzine was served to the patient 4 h after her admission to the ED. This was corrected with at least 2 L of intravenous normal saline boluses. Subsequent EKGs and Sestamibi scan showed no evidence of cardiac ischemia. She was discharged home after a hospital stay of 3 days.

Discussion

We believe this to be the first reported case of myocardial infarction resulting from ingestion of cheese in a patient taking a MAOI. It might be expected that hypertensive crisis could lead to a myocardial infarction, but a review of the medical literature found no such cases reported.     

Ankylosing spondylitis and other inflammatory spondyloarthritis increase the risk of developing type 2 diabetes in an Asian population

This study evaluated whether people with ankylosing spondylitis (AS) and spondyloarthritis are at higher risk of type 2 diabetes mellitus (T2DM). We used a sub-dataset of the National Health Insurance Research Database from 1996 to 2010 to established a AS cohort consisting new patients with AS or spondyloarthritis (N = 7,778) and a non-AS cohort without the diseases (N = 31,112). Incidences of T2DM in the two cohorts, hazard ratios (HRs) of risk of T2DM in association with AS, and cumulative probability of having T2DM were estimated by the end of 2010. The incidence of T2DM was 1.17-fold higher in the AS cohort than in the non-AS cohort (13.5 vs. 11.5, per 1,000 person-years), with an adjusted HR of 1.16 (95 % CI = 1.05–1.29). The T2DM incidence was higher for women than for men; while the Cox model measured sex-specific adjusted HR of T2DM was higher for men than for women. The incidence rate of T2DM increased with age in both cohorts, while the age-specific measures showed that the adjusted HR of T2DM was higher in young AS patients (≤50 years of age) than older ones, compared to their peers of non-AS group. The plot of Kaplan–Meier analysis showed that the overall probability of having T2DM was 2 % higher in the AS cohort than in the non-AS cohort (log-rank test: p < 0.0001). Patients with AS and spondyloarthritis have an increased risk of developing T2DM.