Acute amiodarone liver toxicity likely due to ischemic hepatitis.

BACKGROUND: Hepatotoxicity due to intravenous amiodarone (HIVAD) is a rare side effect with a distinct pattern of enzyme disturbances compared to liver damage from oral amiodarone. Intravenous amiodarone is administered for acute arrhythmias often causing heart failure. The enzyme abnormalities and clinical setting are very similar to that of ischemic hepatitis, a far more common condition. OBJECTIVES: To ascertain if acute HIVAD exists as a separate entity or whether reported cases may be explained by ischemic hepatitis METHODS: In this case-control retrospective study the files of hospitalized patients with markedly elevated aminotransferases were reviewed for the diagnoses of HIVAD or ischemic hepatitis. Medline was searched for published cases of HIVAD. Pooled data of all patients with HIVAD were compared to a control group with ischemic hepatitis. RESULTS: There were no significant differences in the clinical characteristics, laboratory results or histological findings between HIVAD and ischemic hepatitis patients. CONCLUSIONS: In our opinion, there is currently insufficient data to support the existence of distinct HIVAD, and ischemic hepatitis is a more probable diagnosis in most reported cases. Withdrawing amiodarone because of assumed hepatic damage could deprive patients of a life-saving therapy.

Natural cannabinoids suppress the cytokine storm in sepsis-like in vitro model.

Natural cannabinoids may have beneficial effects on various tissues and functions including a positive influence on the immune system and the inflammatory process. The purpose of this study was to investigate the effects of natural cannabinoids on the production of pro-inflammatory cytokines by lipopolysaccharide (LPS)-stimulated whole human blood cells. Levels of the pro-inflammatory cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured before and after exposure of LPS-stimulated whole blood to different concentrations of Cannabidiol (CBD) or a combination of CBD and Tetrahydrocannabinol (THC) extract. LPS stimulated the production of the pro-inflammatory cytokines. Exposure to both CBD and CBD/THC extracts significantly suppressed cytokine production in a dose-dependent manner. Exposure to cannabinoid concentrations of 50 µg/ml or 100 µg/ml resulted in a near-complete inhibition of cytokine production. This study demonstrates that natural cannabinoids significantly suppress pro-inflammatory cytokine production in LPS-stimulated whole blood in a dose-dependent manner. The use of human whole blood, rather than isolated specific cells or tissues, may closely mimic an in vivo sepsis environment. These findings highlight the role that natural cannabinoids may play in suppressing inflammation and call for additional studies of their use as possible novel therapeutic agents for acute and chronic inflammation.

Effect of a four-week course of interleukin-10 on cytokine production in a placebo-controlled study of HIV-1-infected subjects.

Interleukin (IL)-10 suppresses synthesis of the pro-inflammatory cytokines tumor necrosis factor (TNF)alpha, IL-1beta, and interferon (IFN)gamma. Since pro-inflammatory cytokines have been implicated in the production of human immunodeficiency virus type 1 (HIV-1), cytokine synthesis in whole blood cultures were determined during a 4-week course of subcutaneous IL-10 injections in 33 HIV-1-infected patients. Patients were randomized into four groups: placebo (nine), IL-10 at 1 microg/kg/day (nine), IL-10 at 4 microg/kg/day (six) and IL-10 at 8 microg/kg three times per week (nine). Whole blood was obtained at the beginning and conclusion of the study and was stimulated for 24 hours with the combination of IL-18 plus lipopolysaccharide. TNFalpha production in stimulated whole blood was reduced three and six hours after the first injection of IL-10 compared to subjects injected with the placebo. After four weeks of treatment, production of IFNgamma was suppressed in a greater number of patients in the IL-10 treatment groups compared to subjects in the placebo group. Similarly, IL-1beta production was lower in the IL-10 treatment groups compared to subjects receiving placebo. In contrast, after four weeks of IL-10, circulating levels of the anti-inflammatory TNF soluble receptor p55 increased dose-dependently compared to placebo subjects. Patient heterogeneity and small sample size presented difficulties in establishing statistical significance. Although the cytokine changes in our study did not demonstrate statistically significant changes, the data nevertheless reveal that four weeks of IL-10 therapy in HIV-1 infected subjects produced the anticipated suppression of pro-inflammatory cytokines.

Acute renal failure as the presenting symptom of pericardial effusion.

Pericardial effusion from any cause may lead to decreased cardiac output and blood pressure, causing heart failure and reduced renal blood flow. Although pericardial effusion is not uncommon, it is usually not associated with hemodynamic compromise unless the effusion causes cardiac tamponade. Acute renal failure resulting from pericardial effusion is surprisingly rare, with only six cases described to date. We describe the first case known to us of pericardial effusion without tamponade causing acute anuric renal failure. The case was characterized initially by non-specific symptoms and signs; anuria dominated the clinical picture, and was completely reversed after pericardiocentesis.

Healthcare associated infective endocarditis: a distinct entity.

The terms hospital- and community-acquired infections do not cover any longer the full spectrum of acquisition of infection. Consequently, the term healthcare associated infection (HCA) has been recently introduced. In order to examine the applicability of 'HCA infection' to patients with infective endocarditis (IE), 125 episodes of culture-positive IE were categorized into 3 groups of acquisition. 14 (11%) of 125 episodes were defined as hospital acquired (HA) IE (onset of more than 72 h after admission), 52 (42%) as HCA (IE on admission in patients with significant previous healthcare contact), and 59 (47%) as community acquired (CA) (IE on admission in people without recent healthcare contact). 41 (77%) of the 53 causative agents in the HCA IE group were typical nosocomial pathogens, whereas these types of pathogens constituted only 22% (14/64) of the microorganisms in the group of CA IE (p<0.0001). Mortality in the HA and HCA groups combined was significantly higher than that in the CA group (19/62, 31%, vs 6/59, 10%, p=0.01). HCA IE should be recognized as a distinct category that constitutes a large proportion of all cases of IE. HCA IE is significantly different from CA IE and, therefore, may require a different therapeutic approach.