Relationship between elevated bilirubin levels and enhanced warfarin effects during biliary obstruction.

OBJECTIVES: A marked prolongation of the prothrombin time-international normalized ratio (PT-INR) is frequently observed during biliary obstruction in patients using warfarin. The objective of this study was to identify factors associated with PT-INR prolongation during biliary obstruction in patients using warfarin. METHODS: Among 44 patients using warfarin who had biliary obstruction, we retrospectively investigated warfarin doses and laboratory data before and during biliary obstruction. The primary outcome was the association between changes in PT-INR (ΔPT-INR) and changes in laboratory data before and during biliary obstruction. RESULTS: Median PT-INR was 1.59 (IQR 1.38-1.95) before biliary obstruction and 2.27 (IQR 1.60-3.49) during biliary obstruction, indicating significant prolongation during the obstruction (P < 0.001). ΔPT-INR showed strong positive correlations with change in total bilirubin (ΔT-Bil; ρ = 0.692, P < 0.001) and change in conjugated bilirubin (ΔC-Bil; ρ = 0.731, P < 0.001). ΔPT-INR showed a weak negative correlation with the change in albumin (ΔAlb; ρ = -0.371, P < 0.05). When ΔPT-INR was used as the dependent variable in multiple linear regression analysis, ΔT-Bil, ΔC-Bil, and ΔAlb were significantly associated with ΔPT-INR. CONCLUSIONS: PT-INR was prolonged during biliary obstruction in patients using warfarin, and changes in bilirubin levels were associated with ΔPT-INR. If biliary obstruction with markedly elevated bilirubin levels occurs, measuring PT-INR could lead to safer warfarin therapy.

Oral antibiotics and a low-residue diet reduce the incidence of anastomotic leakage after left-sided colorectal surgery: a retrospective cohort study.

PURPOSE: Anastomotic leakage is a potential complication after colorectal surgery. We investigated the effects of oral antibiotics and a low-residue diet on the incidence of anastomotic leakage after left-sided colorectal surgery. METHODS: Outcomes were retrospectively compared between 64 patients who underwent mechanical bowel preparation alone (group A) and 183 patients who underwent mechanical bowel preparation with addition of oral kanamycin and metronidazole (group B) on the day before left-sided colorectal surgery. After surgery, patients in group A received a normal diet containing dietary fiber and those in group B received a low-residue diet. The primary outcome was the incidence of anastomotic leakage. Secondary outcomes were rates of other postoperative complications, length of postoperative hospital stay, and laboratory data. RESULTS: Anastomotic leakage, surgical site infection, and diarrhea were less common in group B than in group A (4.9% vs 18.8%, 6.6% vs 23.4%, and 25.7% vs 43.8%, respectively). Postoperative C-reactive protein levels were significantly lower in group B. The median postoperative hospital stay was significantly shorter in group B than in group A (8 days vs 9 days, P = 0.010). Adaptive double least absolute shrinkage and selection operator regression revealed that use of preoperative oral antibiotics and a postoperative low-residue diet were associated with lower incidence of anastomotic leakage (odds ratio 0.163, 95% confidence interval 0.062-0.430; P < 0.001). CONCLUSION: Oral antibiotics and a low-residue diet reduced the incidence of anastomotic leakage and shortened the postoperative hospital stay by 1 day.

Association of marked prolongation of prothrombin time-international normalized ratio with warfarin and endoscopic nasobiliary drainage for biliary fistula after left hemihepatectomy.

WHAT IS KNOWN AND OBJECTIVE: Vitamin K deficiency is known to cause impaired coagulation. We report a case of marked prolongation of the prothrombin time-international normalized ratio (PT-INR) associated with warfarin and vitamin K deficiency caused by endoscopic nasobiliary drainage (ENBD). CASE PRESENTATION: Oral administration of warfarin was initiated in a 67-year-old man after left hemihepatectomy. He developed a biliary fistula after surgery that was treated by ENBD, which resulted in significant prolongation of the PT-INR. WHAT IS NEW AND CONCLUSION: The effect of warfarin was enhanced in this patient due to reduced absorption of vitamin K as a result of external biliary drainage.

Change in serum ferritin concentration in experimentally induced anemia of chronic inflammation in dogs.

In veterinary medicine, hyperferritinemia is often observed in dogs with various diseases (e.g., histiocytic sarcoma and immune-mediated hemolytic anemia) without evidence of iron overload. The mechanism underlying hyperferritinemia development is not well understood. Anemia caused by inflammation is termed as anemia of chronic disease (ACD), and experimentally induced ACD is known to cause slight hyperferritinemia. However, almost all these studies were based on short-term acute inflammation. Hepcidin, a protein mainly produced by hepatocytes, is thought to be a key regulator in iron release from reticuloendothelial cells (RECs), and its expression is related to ACD. We hypothesized that in the case of long-term ACD, iron deposition in RECs increases through hepcidin, causing a diachronic increase in serum ferritin levels. In the present study, we used a canine model with repeated subcutaneous administration of turpentine oil every 3 days over a period of 42 days (15 injections) and induced long-term inflammatory conditions; furthermore, we evaluated the change in serum ferritin concentration. Hypoproliferative anemia, bone marrow iron deposition and hypoferremia, which are characteristic of ACD, were observed on administering the turpentine injections. Hepatic iron content, hepatic hepcidin mRNA expression and serum ferritin concentration increased during the early period after turpentine injection, but returned to normal levels later. These results show that experimentally induced long-term ACD caused hypoproliferative anemia without sustained increase in hepcidin expression and did not cause systemic iron overload. Thus, chronic inflammation may not contribute greatly to increase in hyperferritinemia.

Cycloartane triterpenes and ingol diterpenes isolated from Euphorbia neriifolia in a screening program for death-receptor expression-enhancing activity.

In our screening program for natural products that increase death-receptor 5 expression, seven new cycloartane triterpenes, euphonerins A-G (1-7), and 3-O-acetyl-8-O-tigloylingol (8), a new ingol diterpene, were isolated from the MeOH extract of Euphorbia neriifolia leaves, together with 3,12-di-O-acetyl-8-O-tigloylingol (9), (24R)-cycloartane-3ß,24,25-triol (10), and three known flavonols (11-13). The structures of 1-8 were elucidated by spectroscopic analysis. Among these compounds, 1-11 showed death-receptor 5 expression enhancing activity.

Cycloartane triterpenes isolated from Combretum quadrangulare in a screening program for death-receptor expression enhancing activity.

In our screening program for natural products that increase DR5 (death-receptor 5) expression, nine new cycloartane triterpenes, combretanones A-G (1-7), combretic acid A (8), and combretic acid B (9), were isolated from a MeOH extract of Combretum quadrangulare leaves. The known oleanane triterpenes (10, 11) and six known flavonols (12-17) were also isolated. The structures of 1-9 were elucidated by spectroscopic studies. Compounds 7, 9, 12, 16, and 17 enhanced DR5 expression, and 16 showed TRAIL-resistance abrogating activity.