Fatal rhabdomyolysis in a patient with liver cirrhosis after switching from simvastatin to fluvastatin

HMG-CoA reductase inhibitors (statins) are widely used to treat hypercholesterolemia. Among the adverse effects associated with these drugs are statin-associated myopathies, ranging from asymptomatic elevation of serum creatine kinase to fatal rhabdomyolysis. Fluvastatin-induced fatal rhabdomyolysis has not been previously reported. We describe here a patient with liver cirrhosis who experienced fluvastatin-induced fatal rhabdomyolysis. This patient had been treated with simvastatin (20 mg/day) for coronary artery disease and was switched to fluvastatin (20 mg/day) 10 days before admission. He was also taking aspirin, betaxolol, candesartan, lactulose, and entecavir. Rhabdomyolysis was complicated and continued to progress. He was treated with massive hydration, urine alkalization, intravenous furosemide, and continuous renal replacement therapy for acute renal failure, but eventually died due to rhabdomyolysis complicated by hepatic failure. In conclusion, fluvastatin should be used with caution in patients with liver cirrhosis, especially with other medications metabolized with CYP2C9.     

Polymorphisms in genes controlling inflammation and tissue repair in rheumatoid arthritis: a case control study

Background  

Various cytokines and inflammatory mediators are known to be involved in the pathogenesis of rheumatoid arthritis (RA). We hypothesized that polymorphisms in selected inflammatory response and tissue repair genes contribute to the susceptibility to and severity of RA.     

Effects of intrathecal bupivacaine in conjunction with hypothermia on neuronal protection against transient spinal cord ischemia in rats

BACKGROUND: Excitotoxic neuronal injury from ischemia may be reduced by local anesthetics. We investigated the neuroprotective effects of intrathecally administered bupivacaine and hypothermia in a rat model of transient spinal cord ischemia. METHODS: PE-10 intrathecal catheter-implanted male Sprague-Dawley rats were randomly assigned to one of four groups: normothermia (NT) and hypothermia (HT) groups (given 15 microl of normal saline) and bupivacaine (B) and bupivacaine-hypothermia (BHT) groups (given 15 mul of 0.5% bupivacaine). Transient spinal cord ischemia was induced by inflation of a 2F Fogarty catheter placed in the aortic arch for 12 min. The rectal temperature was maintained at 37.0 +/- 0.5 degrees C for the NT and B groups, and at 34.5 +/- 0.5 degrees C for the HT and BHT groups. Motor and sensory deficit scores were assessed 2 and 24 h after reperfusion. Lumbar spinal cords were harvested for histopathology and immunoreactivity of heat shock protein 70 (HSP70). RESULTS: After reperfusion, the motor and sensory deficit scores of the NT group were significantly higher than those of the HT (P < 0.05) and BHT (P < 0.001) groups. Significant differences were evident in the motor and sensory deficit scores between the HT and BHT groups at 24 h (P < 0.05). Neuronal cell death and immunoreactivity of HSP70 were frequently observed in the NT and BT groups, but not in the HT and BHT groups. CONCLUSIONS: These results collectively suggest that intrathecal bupivacaine does not provide neuroprotection during normothermic transient spinal cord ischemia in rats, but enhances the neuroprotective effects of hypothermia.     

Characteristics and Treatment Outcomes of Isoniazid Mono-Resistant Tuberculosis: A Retrospective Study

PurposeIsoniazid (INH) mono-resistant tuberculosis (Hr-TB) is a highly prevalent type of drug-resistant TB, possibly associated with unfavorable treatment outcomes. However, definitive guidelines on an optimal treatment regimen and duration for Hr-TB are currently under discussion. We evaluated the characteristics and treatment outcomes of Hr-TB patients.Materials and MethodsWe retrospectively reviewed the medical records of Hr-TB patients treated at a South Korean tertiary referral hospital from January 2005 to December 2018.ResultsWe included 195 Hr-TB patients. 113 (57.9%) were male, and the median age was 56.6 [interquartile range, 40.2–68.6] years. Mutations in katG were the most frequent [54 (56.3%)], followed by those in the inhA [34 (35.4%)]. Favorable and unfavorable outcomes were noted in 164 (84.1%) and 31 (15.9%) patients, respectively. Smoking history [odds ratio (OR)=5.606, 95% confidence interval (CI): 1.695–18.543, p=0.005], low albumin level (OR=0.246, 95% CI: 0.104–0.578, p=0.001), and positive acid-fast bacilli culture at 2 months (OR=7.853, 95% CI: 1.246–49.506, p=0.028) were associated with unfavorable outcomes.ConclusionA tailored strategy targeting high-risk patients is imperative for improved treatment outcomes. Further research on the rapid and accurate detection of resistance to INH and other companion drugs is warranted.     

Asthma Attack Associated with Oxidative Stress by Exposure to ETS and PAH

Asthma is primarily an airways inflammatory disease, and the bronchial airways have been shown to be particularly susceptible to oxidant-induced tissue damage. Objective. The purpose of this study was to investigate whether pulmonary inflammation in asthma is associated with exposure to environmental oxidants such as polycyclic aromatic hydrocarbon (PAH) and environmental tobacco smoke (ETS). Method. We assessed the exposure level of PAH and ETS by using urinary 1-hydroxypyrene glucuronide (1-OHPG) and cotinine. We estimated oxidative damage and inflammatory cytokine levels from 16 asthma patients and 16 patients in stable conditions 1 to 2 months later. Results. Our study showed that the levels of oxidative damage, as measured by malondialdehyde (MDA), were significantly increased (p = 0.006) during the asthma attacks. Proinflammatory and anti-inflammatory cytokines were both increased during the asthma attacks compared to the stable conditions at follow-up. Interleukin (IL-6) and IL-10 were especially increased significantly (p = 0.015 and p < 0.001, respectively). Correlations were observed between inflammatory cytokines such as IL-6 and IL-1β (p = 0.034). Conclusion. This study supports the results of in vitro studies that oxidative stress, specifically lipid peroxidation, contributes to the pathophysiology of asthma. Therefore, environmental interventions based on this better understanding are needed to significantly reduce oxidant stress and prevent or minimize the development of asthmatic symptoms.     

Higher serum bilirubin level as a protective factor for the development of diabetes in healthy Korean men: A 4 year retrospective longitudinal study

Objective

Bilirubin, a natural product of heme catabolism by heme oxygenase, one of key antioxidant enzymes, has been recognized as a substance with potent antioxidant and cytoprotective properties. Several studies have shown a significant negative relationship between serum bilirubin levels and the risk of metabolic disorders, including type 2 diabetes. However, longitudinal studies investigating the association of elevated serum bilirubin levels and type 2 diabetes are lacking. In the present study, we aimed to investigate the longitudinal effects of baseline serum bilirubin concentrations on the development of type 2 diabetes in healthy Korean men.

Materials and Methods

This 4 year retrospective longitudinal observational study was conducted at the Asan Medical Center, Seoul, Republic of Korea. The study population consisted of 5960 men without type 2 diabetes who underwent routine health examinations in 2007 (baseline) and 2011 (follow-up). Baseline serum bilirubin concentrations were determined by the vanadate oxidation method.

Results

During a 4 year period, 409 incident cases of diabetes (6.9 %) were identified. Incident type 2 diabetes decreased across the baseline bilirubin quartile categories (P for trend < 0.001). In multivariable-adjusted model, the relative risk (RR) for the development of type 2 diabetes was significantly lower in the highest (i.e., 1.30–2.00 mg/dl) than in the lowest bilirubin quartile category (i.e., ≤ 0.90 mg/dl), even after adjustment for confounding variables (RR = 0.69, 95% confidence interval 0.48–0.99, P for trend = 0.041).

Conclusions

The results indicate that serum total bilirubin level may provide additional information for predicting future development of type 2 diabetes in healthy subjects.     

Murine thymocytes proliferate in direct response to interleukin-7

The ability of interleukin-7 (IL-7) to stimulate murine thymocyte proliferation was investigated. IL-7, either alone or in concert with lectin, induced proliferation of adult thymocytes as well as day 13 fetal and adult CD4-/CD8-thymocytes. The IL-7-induced proliferative response of unfractionated thymocytes could not be inhibited by antibodies to IL-2, or IL-4, IL-6, or the IL-2 receptor. In addition, IL-2, IL-4, and IL-6 were not produced by thymocytes activated with IL- 7, as judged by the absence of biologically active cytokine in IL-7- stimulated culture supernatants. IL-7 could act in concert with IL-2 and IL-4 or with IL-4 to enhance the proliferative response of thymocyte cultures. Thus, IL-7 may cause proliferation of thymocytes directly, not indirectly, through production of IL-2, IL-4, or IL-6. IL- 7 may then play a significant role in differentiation of T lymphocytes.     

Role of CD56-expressing immature biliary epithelial cells in biliary atresia

AIM: To analyze the clinical and pathological parameters and expression of the neural cell adhesion molecule(CD56) in patients with biliary atresia(BA).METHODS: Established clinical laboratory markers of hepatic function, including enzyme activity, protein synthesis, and bilirubin metabolism, were evaluated in patients with BA and compared with those in patients with choledochal cysts and neonatal hepatitis. Pathological changes in tissue morphology and fibrosis were examined by histological and tissue collagen staining. Immunohistochemical staining for the biliary epithelial cell markers CD56 and CK19 together with the Notch signaling related molecules Notch1 and Notch2 was performed in the context of alterations in the structure of intrahepatic biliary ducts.RESULTS: Differences in some clinical laboratoryparameters among the three diseases examined were observed, but they did not correlate with the pathological classification of fibrosis in BA. Immunohistochemical staining showed the presence of CD56-positive immature bile ducts in most patients(74.5%) with BA but not in patients with choledochal cysts or neonatal hepatitis. The number of CD56-expressing cells correlated with disease severity, with more positive cells present in the later stages of liver damage(81.8% vs 18.2%). Furthermore, bile plugs were mainly found in CD56-positive immature biliary ducts. Notch signaling was a key regulatory pathway in biliary duct formation and played a role in tissue fibrosis. Notch1 was co-expressed in CD56-positive cells, whereas Notch2 was found exclusively in blood vessels in the portal area of patients with BA. CONCLUSION: The maturation of biliary epithelial cells and the expression of Notch may play a role in the pathogenesis of BA.