Serum Bilirubin Concentration Research Articles

Pregnancy course in patients with intrahepatic cholestasis of pregnancy treated with very low doses of ursodeoxycholic acid

Objective. Ursodeoxycholic acid (UDCA) has been proposed as the optimal pharmacological treatment for intrahepatic cholestasis of pregnancy (ICP). The lowest effective dosage of UDCA in women with ICP has not been established. The objective is to determine the risk of adverse pregnancy outcomes resulting from ICP and to measure changes in liver function parameters and pruritus severity in ICP patients treated with low doses of UDCA. Material and methods. ICP was diagnosed in 203 patients on the basis of pruritus and elevated liver biochemical parameters. Patients with total bile acids (TBA) ≥10 μmol/l (n = 157) received UDCA (300–450 mg/day; 4–6 mg/kg/day) until delivery. Maternal and fetal outcomes of women with ICP were compared with 100 patients without cholestasis. Patients with ICP were hospitalized for treatment and fetal surveillance. Results. There was no correlation between fetal and neonatal complication rates in ICP patients and biochemical markers of cholestasis. Significant declines in serum TBA (p = 0.003), bilirubin concentration (p = 0.026) and aminotransferase activity (p < 0.001) were observed during treatment with low doses of UDCA. Moreover, severity of pruritus was ameliorated during the 2 weeks of therapy (p = 0.037). A total of 17 patients (10.9%) did not respond to treatment. Conclusions. UDCA at low doses improved biochemical markers and clinical symptoms in almost 90% of ICP patients.

Thromboelastographic Evaluation of Dogs with Acute Liver Disease.

BackgroundGiven the liver's pivotal role in hemostasis and fibrinolysis, the coagulopathy accompanying hepatic disease is complex.Hypothesis/ObjectivesTo prospectively evaluate kaolin‐activated thromboelastography (TEG) in dogs with acute liver disease (ALD) and compare with plasma‐based coagulation tests.AnimalsTwenty‐one dogs with a diagnosis of ALD based on recent onset of clinical signs accompanied by increases in serum bilirubin concentration and alanine aminotransferase activity.MethodsClinical presentation, CBC, serum biochemistry, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and TEG analysis were evaluated in 21 dogs with a subset also having fibrinogen, antithrombin (AT) activity, protein C (PC) activity, d‐dimers, and von Willebrand's factor (vWF) activity analyzed. A PT >1.5 times the upper limit of normal defined acute liver failure (ALF).ResultsDogs with ALD had mean increases in R, K, LY30, PT, aPTT, and vWF activity, and decreases in angle, maximal amplitude (MA), G, AT activity, and PC activity. The TEG results defined dogs as hypocoagulable (11/21), normocoagulable (8/21), or hypercoagulable (2/21). Increases in LY30 defined 8/21 dogs as hyperfibrinolytic. Hypocoagulable and hyperfibrinolytic dogs had lower fibrinogen and PC activity than dogs without these abnormalities. Overall, ALF dogs had greater increases in K and LY30, and decreases in MA, G, and PC activity than dogs with less severe hepatic impairment. Results for MA and LY30 were positively correlated with serum bilirubin concentration and white blood cell count, and negatively correlated with serum cholesterol concentration.Conclusions and Clinical Importance ALD dogs have a range of coagulation abnormalities that trend toward hypocoagulability and hyperfibrinolysis as functional impairment occurs.

Serum Bilirubin and Disease Progression in Mild COPD

COPD is a chronic inflammatory disorder associated with oxidative stress. Serum bilirubin has potent antioxidant actions, and higher concentrations have been shown to protect against oxidative stress. The relation between serum bilirubin and COPD progression is unknown. Serum bilirubin was measured in 4,680 smokers aged 35 to 60 years old with mild to moderate airflow limitation. The relationship of serum bilirubin to postbronchodilator FEV₁ and rate of FEV1 decline over 3 to 9 years was determined using regression modeling. Total and disease-specific mortality were also ascertained. Serum bilirubin was positively related to FEV₁ (P < .001). Serum bilirubin was also negatively related to the annual decline in FEV₁ when adjusted for baseline demographics, pack-years smoked, and baseline measures of lung function (P = .01). Additionally, serum bilirubin was negatively associated with risk of death from coronary heart disease (P = .03); however, the relationships between bilirubin and other mortality end points were not statistically significant (P > .05). Bilirubin is inversely related to COPD disease severity and progression. Higher serum bilirubin concentration was associated with a higher FEV₁ and less annual decline in FEV₁. Bilirubin was also associated with less coronary heart disease mortality. These data support the hypothesis that bilirubin has a protective effect on COPD disease progression, possibly through its antioxidant actions. Bilirubin may prove useful as an easily accessible and readily available blood-based COPD biomarker.

Association of serum total bilirubin with renal outcome in Japanese patients with stages 3–5 chronic kidney disease

ObjectiveSerum bilirubin has been reported to be associated with the progression of kidney disease in patients with diabetic nephropathy. Less is known, however, about the relationship between bilirubin and chronic kidney disease (CKD) of other etiologies. This study was designed to clarify whether serum total bilirubin concentration is associated with kidney disease progression in patients with CKD independent of etiology. Materials and methodsThis prospective observational study enrolled 279 consecutive patients with stages 3–5 CKD. The renal endpoint was the composite of the doubling of serum creatinine or end-stage renal disease requiring dialysis. Patients were divided into three groups by their serum total bilirubin concentrations: ≤0.3 (lowest), 0.4–0.5 (middle), and ≥0.6 (highest) mg/dL. A Cox proportional hazards model was applied to determine the risk factors for poor renal outcome. ResultsThe median follow-up period was 21months. One-hundred and three patients reached renal end points. After multivariable adjustment, a 0.1mg/dL increase in serum bilirubin was associated negatively with poor renal outcome (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.60–0.87). In addition, after adjustment for confounding factors, including traditional and nontraditional cardiovascular risk factors, the middle (HR 3.14, 95% CI 1.36–8.57) and lowest (HR 4.22, 95% CI 1.81–11.59) bilirubin groups had significantly higher HRs for renal outcome than the highest bilirubin group. ConclusionsLower serum bilirubin concentration was independently associated with adverse renal outcomes, suggesting that the measurement of serum bilirubin is useful for predicting kidney disease progression in patients with moderate to severe CKD.

Comparison of the safety and efficacy of a fixed-dose combination regimen and separate formulations for pulmonary tuberculosis treatment

OBJECTIVES:Fixed-dose combination formulations, which simplify the administration of drugs and prevent the development of drug resistance, have been recommended as a standard anti-tuberculosis treatment regimen. However, the composition and dosage recommendations for fixed-dose combination formulations differ from those for separate formulations. Thus, questions about the effectiveness and side effects of combination formulations remain. The aim of this study was to compare the safety and efficacy of these two types of anti-tuberculosis regimens for pulmonary tuberculosis treatment.METHOD:A prospective, randomized controlled study was conducted using the directly observed treatment short-course strategy. Patients were randomly allocated to one of two short-course regimens. One year after completing the treatment, these patients' outcomes were analyzed. ClinicalTrials.gov: NCT00979290.RESULTS:A total of 161 patients were enrolled, 142 of whom were evaluable for safety assessment. The two regimens had a similar incidence of adverse effects. In the per-protocol population, serum bilirubin concentrations at the peak level, at week 4, and at week 8 were significantly higher for the fixed-dose combination formulation than for the separate formulations. All patients had negative sputum cultures at the end of the treatment, and no relapse occurred after one year of follow-up.CONCLUSIONS:In this randomized study, transient higher serum bilirubin levels were noted for the fixed-dose combination regimen compared with the separate formulations during treatment. However, no significant difference in safety or efficacy was found between the groups when the directly observed treatment short-course strategy was used.

To study inverse relationship between serum total bilirubin levels and severity of disease in patients with stable coronary artery disease as assessed by coronary angiography and syntax score

ObjectivesMany studies have shown that bilirubin may protect against atherosclerosis. Lipid oxidation and formation of oxygen radicals are important elements of arterial plaque formation and atherosclerosis, and are involved in the pathophysiology of coronary artery disease (CAD). Because bilirubin has antioxidant properties, it has been suggested that it may have a protective role in the atherosclerotic process. In the present study, we assess the association between serum total bilirubin levels and the severity of CAD as assessed by angiography and Syntax score. MethodsThis is a prospective study which included Patients who underwent coronary angiography for Chronic stable angina pectoris (CSAP) from august 2013 to July 2014 at our centre. Serum bilirubin levels were determined. The patients were divided into tertiles according to their Syntax score and biirubin levels were analysed. ResultsTotal of 319 patients were registered for the study. The total bilirubin levels in the low Syntax score group were significantly higher than those of the other groups. serum bilirubin levels were identified as independent correlates of a high Syntax score and severity of cad. ConclusionsSerum bilirubin concentrations in the upper portion of the reference value (0.61–1.0 mg/dl) reduce atherogenic risk and provide protection against CAD. In contrast, serum bilirubin concentrations in the lower portion of the reference value (0–0.60 mg/dl) may be associated with increased risk of CAD. The evidence presented in our study supports the concept that bilirubin, via its antioxidant potential, has antiatherogenic properties and that an inverse relationship exists between circulating bilirubin concentrations and risk of CAD.

Prolonged intra-aortic balloon pump support in biventricular heart failure induces right ventricular reverse remodeling

BackgroundRight ventricular dysfunction is associated with high morbidity and mortality in candidates for left ventricular assist device (LVAD) implantation or cardiac transplantation. MethodsWe examined the effects of prolonged intra-aortic balloon pump (IABP) support on right ventricular, renal and hepatic functions in patients presenting with end-stage heart failure. ResultsBetween March 2008 and June 2013, fifteen patients (mean age=49.5years; 14 men) with end-stage systolic heart failure (HF), contraindications for any life saving procedure (conventional cardiac surgery, heart transplantation, LVAD implantation) and right ventricular dysfunction were supported with the IABP. The patients remained on IABP support for a mean of 73±50days (median 72, range of 13–155). We measured the echocardiographic and hemodynamic changes in right ventricular function, and the changes in serum creatinine and bilirubin concentrations before and during IABP support. Mean right atrial pressure decreased from 12.7±6.5 to 3.8±3.3 (P<0.001) and pulmonary artery pressure decreased from 35.7±10.6 to 25±8.4mmHg (P=0.001), while cardiac index increased from 1.5±0.4 to 2.2±0.7l/m2/min (P=0.003) and right ventricular stroke work index from 485±228 to 688±237mmHg×ml/m2 (P=0.043). Right ventricular end-diastolic diameter decreased from 34.0±6.5mm to 27.8±6.2mm (P<0.001) and tricuspid annular systolic tissue Doppler velocity increased from 9.6±2.4cm/s to 11.1±2.3cm/s (P=0.029). Serum creatinine and bilirubin decreased from 2.1±1.3 to 1.4±0.6mg/dl and 2.0±1.0 to 0.9±0.5mg/dl, respectively (P=0.002 and P<0.001, respectively). ConclusionsProlonged IABP support of patients presenting with end-stage heart failure and right ventricular dysfunction induced significant improvement in right ventricular and peripheral organ function.

Progression to high-risk gastroesophageal varices in children with biliary atresia with low-risk signs at first endoscopy.

Biliary atresia carries a risk of bleeding because of portal hypertension. Our goal was to define the factors associated with the emergence of endoscopic signs carrying a high risk of bleeding in children who did not display these signs at the first upper gastrointestinal endoscopy. From 1989 to 2013, a total of 225 children with low-risk signs at the first endoscopic examination underwent ≥2 upper gastrointestinal endoscopic examinations. The emergence of high-risk gastroesophageal varices was observed in 76 children in the 10 years following the first endoscopic examination. A survival study using the occurrence of high-risk varices as an event was performed to identify factors related to the emergence of these varices and to describe the probability of their emergence in 2 groups of children ages older than 18 months and 18 months or younger at the time of the first endoscopy. High total serum bilirubin concentration, young age, and high number/grade of esophageal varices at the first endoscopy were significantly related to the emergence of high-risk varices. The probability of the emergence of high-risk signs was higher and these signs appeared faster in infants 12 months of age or younger and/or when the first endoscopic examination displayed >1 grade 1 or grade 2 varices. Progression to high-risk varices was also related to bilirubinemia in children older than 18 months at the first endoscopy. The results allow defining a program of repeat endoscopies to detect high-risk varices and to discuss endoscopic primary prophylaxis of bleeding or hasten liver transplantation when these signs are found.

Bilirubin: striking gold in diabetic vasculopathy?

Vascular complications are the primary cause of morbidity and mortality and a major contributor to health care costs in patients with diabetes (1). While the etiology of vascular disease is multifactorial, endothelial dysfunction characterized by a decrease in nitric oxide (NO) synthesis from endothelial NO synthase (eNOS) and blunted endothelium-dependent vasodilation is a seminal feature in diabetes-associated vascular disease. Given the dramatic increase in the incidence of diabetes worldwide, there is an urgent need for new therapies that targets this cellular defect in diabetes. Although long considered a toxic waste product of heme metabolism, the yellow pigment bilirubin is now recognized as an important vasoprotective molecule. Bilirubin is formed by the action of inducible heme oxygenase-1 (HO-1) or constitutively expressed HO-2, which degrades heme into biliverdin, carbon monoxide (CO), and iron (Fig. 1). Biliverdin is rapidly reduced to bilirubin by biliverdin reductase (BVR). Bilirubin is further processed in the liver, where it is conjugated with glucuronic acid by uridine diphosphate-glucuronosyltransferase A1A (UGT1A1) to a water-soluble form for elimination. While early work identified the potent antioxidant properties of bilirubin, more recent studies found that bilirubin elicits anti-inflammatory and antiapoptotic effects in endothelial cells and improves endothelium-dependent vasodilation in murine hypercholesterolemic blood vessels (2–5). Clinical studies also support a protective role, as serum bilirubin concentrations show an inverse relationship with risk for a constellation of cardiovascular disorders (6). Interestingly, serum bilirubin levels are lower …

Clinical significance of serum bilirubin and gamma-glutamyltransferase levels on coronary atherosclerosis assessed by multidetector computed tomography

Background and aimsLow bilirubin and high gamma-glutamyltransferase (GGT), which are endogenous markers of oxidative stress, confer a higher risk of cardiovascular disease (CVD). We investigated associations between serum concentrations of bilirubin, GGT and coronary atherosclerosis. Methods and resultsA cross-sectional analysis was performed on 1520 subjects who underwent multidetector computed tomography scans. Coronary atherosclerosis was assessed by coronary artery calcium score (CACS) and obstructive coronary artery disease (OCAD), was defined as the presence of coronary artery stenosis of ≥50%. Total bilirubin (TB) level was negatively correlated with CACS and coronary stenosis whereas GGT level was positively correlated with CACS in men. However, there was no correlation between TB, GGT levels and either CACS or coronary artery stenosis in women. In a multivariate-adjusted model, TB level was inversely associated with a CACS > 100 [odds ratio (OR) per log standard deviation (SD), 0.67; 95% confidence interval (CI), 0.52–0.87], and OCAD (OR per log SD, 0.77; 95% CI, 0.62–0.95) in men. By contrast, GGT level was positively associated with a CACS > 100 (OR per log SD, 1.35; 95% CI, 1.05–1.73) but not with OCAD. Adding TB and GGT to the conventional risk factors increased predictive accuracy for CACS > 100 (net reclassification improvement index [NRI] = 13.1%, P = 0.026; integrated discrimination index [IDI] = 0.024, P = 0.001) and for OCAD (NRI = 12.6%, P = 0.026; IDI = 0.010, P = 0.013). ConclusionsLow TB and high GGT levels were concomitantly associated with coronary atherosclerosis in Korean men. Future studies are needed to elucidate the causal associations of TB and GGT with CVD.

Feeding soy protein isolate and n-3 PUFA affects polycystic liver disease progression in a PCK rat model of autosomal polycystic kidney disease.

In polycystic liver disease (PCLD), multiple cysts cause liver enlargement, structural damage, and loss of function. Soy protein and dietary ω-3 polyunsaturated fatty acids (n-3 PUFAs) have been found to decrease cyst proliferation and inflammation in polycystic kidney disease. Therefore, the aim of the study was to investigate whether soy protein and n-3 PUFA supplementation attenuates PCLD. Young (age 28 days) female PCK rats were fed (n = 12 per group) either casein + corn oil (casein + CO), casein + soybean oil (casein + SO), soy protein isolate + soybean oil (SPI + SO), or SPI + 1:1 soybean/salmon oil blend (SPI + SB) diet for 12 weeks. Liver histology, gene expression by real-time quantitative polymerase chain reaction, and serum markers of liver injury were determined. Diet had no effect on PCLD progression as indicated by no significant differences in liver weight and hepatic proliferation gene expression between diet groups. PCK rats fed SPI + SB diet, however, had the greatest (P < 0.05) histological evidence of hepatic cyst obstruction, portal inflammation, steatosis, and upregulation (P = 0.03) of fibrosis-related genes. Rats fed SPI + SB diet also had the lowest (P < 0.001) serum cholesterol and higher (P < 0.05) serum alkaline phosphatase and bilirubin concentrations. Feeding young female PCK rats SPI and n-3 PUFA failed to attenuate PCLD progression. Furthermore, feeding SPI + SB diet resulted in complications of hepatic steatosis attributable to cysts obstruction of bile duct and hepatic vein. Based on the results, it was concluded that diet intervention alone was not effective at attenuating PCLD associated with autosomal recessive polycystic kidney disease.

Post-hepatectomy liver failure in patients with colorectal liver metastases.

Liver resection remains the standard treatment for colorectal liver metastases (CLM). Major hepatic resection is now performed frequently and with relative safety, but postoperative mortality is still reported to occur in up to 6 % of the patients with CLM undergoing liver resection even at high-volume centers. Post-hepatectomy liver failure (PHLF) is a key factor involved in mortality. The frequency of PHLF is reported to be 1-16 %, and has varied greatly among studies since a clear definition of PHLF has been lacking. Recently, the International Study Group of Liver Surgery (ISGLS) proposed a simple definition of PHLF, which includes the combination of the severity of PHLF and does not use an arbitrary cut-off value for the serum bilirubin concentration and INR. Hence, it may be the most useful definition in the clinical setting. Advanced age, a small future liver remnant volume, preoperative chemotherapy and chemotherapy-induced liver injury may all be associated with PHLF. Once PHLF occurs, it is difficult to reverse, and thus, strategies aimed at prevention are keys to reducing the mortality after liver surgery.

Acute alcohol consumption elevates serum bilirubin: An endogenous antioxidant

BackgroundModerate alcohol consumption has been associated with both negative and favorable effects on health. The mechanisms responsible for reported favorable effects remain unclear. Higher (not necessarily elevated) concentrations of serum bilirubin, an antioxidant, have also been associated with reduced risk of cardiovascular disease and all-cause mortality. This study tests the hypothesis that single dose alcohol consumption elevates bilirubin providing a potential link between these observations. Methods18 healthy individuals (eight cigarette smokers) were administered alcohol, calibrated to achieve blood concentrations of 20, 80 and 120mg/dL, in random order in three laboratory sessions separated by a week. Each session was preceded by and followed by 5–7 days of alcohol abstinence. Serum bilirubin was measured at 7:45a.m. prior to drinking, at 2p.m., and at 7:45 the next morning. Mixed effects regression models compared baseline and 24h post-drinking bilirubin concentrations. ResultsTotal serum bilirubin (sum of indirect and direct) concentration increased significantly after drinking from baseline to 24h in non-smokers (from M=0.38, SD=0.24 to M=0.51, SD=0.30, F(1,32.2)=24.24, p<.0001) but not in smokers (from M=0.25, SD=0.12 to M=0.26, SD=0.15, F(1,31.1)=0.04, p=0.84). In nonsmokers the indirect bilirubin concentration and the ratio of indirect (unconjugated) to direct (conjugated) bilirubin also increased significantly. ConclusionsAlcohol consumption leads to increases in serum bilirubin in nonsmokers. Considering the antioxidant properties of bilirubin, our findings suggest one possible mechanism for the reported association between alcohol consumption and reduced risk of some disorders that could be tested in future longitudinal studies.

Low serum total bilirubin concentration in patients with type 1 diabetes mellitus complicated by retinopathy and nephropathy

Aims Although a relationship between serum bilirubin concentration and diabetic microangiopathy in patients with type 2 diabetes has been reported, whether such a relationship exists in patients with type 1 diabetes is unknown. This study assessed the relationships between serum total bilirubin concentration and retinopathy/nephropathy in patients with type 1 diabetes.

The duration of diabetes is inversely associated with the physiological serum bilirubin levels in patients with type 2 diabetes.

The aim of this study was to assess the relationship between the duration of diabetes and the physiological serum bilirubin concentration in association with antioxidant properties in patients with type 2 diabetes. A total of 1,746 patients with type 2 diabetes were investigated in this cross-sectional study. An analysis of covariance was performed after adjusting for other covariates. Simple correlation analyses and a multivariate regression model were used to assess the association between the duration of diabetes and the serum bilirubin concentration. The mean total bilirubin value differed significantly according to the tertile of diabetes duration (<5 years, 12.38 μmol/L, 95% confidence interval (CI) 12.02-12.76; 5-11.9 years, 12.33 μmol/L, 95% CI 11.97-12.69; ≥12 years, 11.73 μmol/L, 95% CI 11.35-12.11; p for trend =0.033), after adjustment for other covariates. In addition, an inverse correlation was found between the serum bilirubin concentration and diabetes duration (ρ=-0.211, p<0.001). According to a multivariate model, the association between the diabetes duration and serum bilirubin concentration remained significant, even after adjustment for confounding factors (β=-0.074, p=0.008). The duration of diabetes is inversely associated with a serum bilirubin concentration within the physiologic range in patients with type 2 diabetes.

The relationship between serum bilirubin concentration and coronary artery ectasia.

IntroductionThe pathophysiology of coronary artery ectasia (CAE) has not been clearly identified, although multiple abnormalities including arteritis, endothelial dysfunction, and atherothrombosis have been reported. Several studies have demonstrated that higher serum bilirubin inhibits the inflammation and proliferation of vascular smooth muscle cells; also there is a relationship between serum bilirubin and cardiovascular disease. However, the relationship between bilirubin and CAE is still unknown.AimWe compared serum bilirubin concentration between CAE patients and controls.Material and methodsThis study included 50 CAE patients (20 male, mean age: 60.26 ±10.6 years) and 30 control persons (10 male, mean age: 57.86 ±11.6 years). These participants underwent concurrent routine biochemical tests and leukocyte count, hemoglobin, hematocrit and platelet count in whole blood. These parameters were compared between groups.ResultsNo statistically significant difference was found between the two groups in terms of basic characteristics. Total, direct and indirect serum bilirubin levels were significantly lower among persons with CAE patients than controls (0.37 ±0.4 vs. 0.71 ±0.6 and 0.13 ±0.1 vs. 0.27 ±0.2 and 0.24 ±0.2 vs. 0.43 ±0.4 mg/dl; all p<0.001, respectively).ConclusionsOur study revealed a relationship between serum bilirubin and CAE.

Lower serum levels of bilirubin in the newly diagnosed lung cancer patients: A case-control study in China.

A few prospective studies demonstrated that bilirubin levels were inversely associated with the risk of lung cancer. However, the retrospective study about the relationship between bilirubin levels and lung cancer in China was not available. So, we want to know whether there has a difference in serum bilirubin concentrations between normal people and lung cancer patients. Using a case-control study, we investigated the bilirubin levels in 317 patients with lung cancer and 317 age-, sex-matched controls from Zhejiang Cancer Hospital. Furthermore, we analyzed the associations between serum bilirubin expressions and baseline clinical features of lung cancer patients using a Wilcoxon rank sum test. Bilirubin levels, including total bilirubin, direct bilirubin, and indirect bilirubin, were significantly lower in human lung cancer serum relative to normal control (P < 0.001), and the older (> 50 years) had higher bilirubin levels compared with the younger (27-50 years) in lung cancer group. Besides, the duration of smoking was negatively related to bilirubin levels, but they did not reach statistical significance except for indirect bilirubin (P = 0.041). However, there was no difference in bilirubin levels between small cell lung cancer (SCLC) and non-SCLC (NSCLC), and we did not find that the bilirubin levels were correlated with sex, drinking status in patients of lung cancer. Serum total bilirubin, indirect bilirubin, and direct bilirubin levels of the patients with lung cancer were all significantly lower than those of control group (P < 0.001). Lower levels of bilirubin may be a risk factor for lung cancer, and it could serve as a potential screening biomarker for lung cancer. Large-scale investigations and additional improvements are urgently needed to demonstrate the mechanism and molecular pathway in order to achieve the clinical utility in the future.

Routine administration of intravenous calcium during exchange blood transfusion for treatment of severe neonatal hyperbilirubinaemia: a systematic review of quantitative evidence protocol.

The objective of this review is to assess the effectiveness of intravenous calcium given during exchange blood transfusion (EBT) in neonates.More specifically, the objectives of the review are to determine whether: Neonatal hyperbilirubinaemia is an abnormally high level of bilirubin in the circulating blood, resulting in clinically visible icterus or jaundice. A serum bilirubin level above 5 mg per dL (86 μmol per L) is a frequently encountered problem worldwide and is a common reason for neonates to present to the emergency department.Unconjugated bilirubin is toxic to infants' brains when the concentration exceeds a certain level. An unconjugated serum bilirubin concentration at toxicity level is described as 'severe hyperbilirubinaemia'. The concentrations that define toxic level vary, depending on the gestational age of the neonates and fetal maturity.Severe hyperbilirubinaemia can cause encephalopathy if not promptly treated, with significant complications such as athetoid cerebral palsy, sensorineural hearing loss, paralysis of upward gaze, dental enamel dysplasia and death.Recent reports indicate that these conditions, though rare, are still occurring despite the availability of efficient methods for treatment of hyperbilirubinaemia and its prevention.These complications can be prevented if the level of bilirubin is reduced rapidly with exchange blood transfusion.Exchange blood transfusion (EBT) is the most rapid and effective method for lowering serum bilirubin concentrations, but it is rarely needed when intensive phototherapy is effective.In the presence of hemolytic disease, severe anaemia, or a rapid rise in the total serum bilirubin level (greater than 1 mg per dL per hour in less than six hours), EBT is the recommended treatment. EBT also removes partially hemolyzed and antibody-coated erythrocytes and which is then replaced with uncoated donor red blood cells. If intensive phototherapy fails to lower the bilirubin level, then EBT is always considered as the next line of treatment in any newborn with non-hemolytic jaundice.Complications of EBT can include hypocalcaemia, seizures and even death within 24 hours. The potential seriousness of these complications makes clinicians consider intensive phototherapy before EBT.However, the option of intensive phototherapy may not be feasible and could be quite ineffective in resource limited settings where the required facilities and electrical power supply are inadequate. Under these circumstances neonates with severe hyperbilirubinaemia will most likely be treated with EBT.Exchange transfusion of blood collected with acid-citrate-dextrose (ACD) containing bags may produce hypocalcaemia.To decrease the morbidity from chelation of divalent cations by citrate, routine administration of calcium gluconate during EBT was advocated,but tetany, convulsion and death may still occur when ACD blood is used.However, there are controversies about the effectiveness of intravenous calcium in reducing these calcium-related morbidities. A preliminary search for systematic reviews in MEDLINE, the Cochrane Library, Campbell Library and the Joanna Briggs Database of Systematic Reviews and Implementation Reports failed to identify any existing publications on this topic. As a result, this review will examine current quantitative evidence regarding the effectiveness of routine administration of intravenous calcium during EBT in the treatment of severe hyperbilirubinaemia, with specific aim to describe incidences of hypocalcaemia, seizures and deaths after such a transfusion.

Effect of taurine on attenuating chemotherapy-induced adverse effects in acute lymphoblastic leukemia.

The purpose of our study was to evaluate the effect of oral taurine supplementation on the incidence of chemotherapy-induced adverse drug reactions during chemotherapy in young adults with acute lymphoblastic leukemia (ALL). Forty young adult (aged over 16 years) with ALL, at the beginning of maintenance course of their chemotherapy, were recruited to the study. The study population was randomized in a double blind manner to receive either taurine or placebo. Life quality and adverse drug reactions were assessed using questionnaire. Blood cell count, hemoglobin (Hb), hematocrit (Hct), serum bilirubin, transaminases, urea, and creatinine concentrations were evaluated. Data was analyzed using Statistical Package for Social Sciences (SPSS) software. Of total participants, 43.8% were female and 56.3% were male. The mean age was 19.16 ± 1.95 years (range: 16-23 years). The results indicated that the levels of white blood cells were significantly (P < 0.05) increased in taurine treated group, but other hematological values did not differ significantly in either group. Taurine administration improved liver and kidney functions, indicated by decline of serum bilirubin, transaminases, urea, and creatinine, respectively in comparison to the controls (P < 0.05). Moreover, taurine significantly reduced serum malondialdehyde (MDA) and superoxide dismutase (SOD) levels (P < 0.05). In conclusion our results indicated that taurine supplementation could be a protection against chemotherapy-induced toxicities probably by its antioxidant capacity. Present study showed effectiveness of taurineon the chemotherapy-related toxicities and some of the complications during the maintenance period of treatment following coadministration in young adults with ALL.

Role of Bilirubin in Diabetic Vascular Complications: Can Bilirubin Predict More than Just Liver Disease?

Role of Bilirubin in Diabetic Vascular Complications: Can Bilirubin Predict More than Just Liver Disease?