[Show abstract][Hide abstract] ABSTRACT: Despite recent progress in Critical Care Medicine, sepsis is still a major medical problem with a high rate of mortality and morbidity especially in intensive care units. Oxidative stress induced by inflammation associated with sepsis causes degradation of heme protein, increases microsomal free heme content, promotes further oxidative stress and results in cellular and organ damage. Heme-oxygenase-1 (HO-1) is a rate-limiting enzyme for heme breakdown. HO-1 breaks down heme to yield CO, iron and biliverdin. Measurement of CO in exhaled air may potentially be useful in monitoring changes in HO enzyme activity in vivo, which might reflect the degree of inflammation or oxidative stress in patients with systemic inflammation. The increased exhaled CO concentrations were observed after anesthesia/surgery, in critically ill patients and also in systemic inflammation/sepsis. Some reports also showed that exhaled CO concentration is related to mortality. Further studies are needed to elucidate whether increased endogenous CO production may predict a patient's morbidity and mortality. Techniques for monitoring CO are continuously being refined and this technique may find its way into the office of clinicians.
Journal of Breath Research 12/2010; 4(4):047103. · 2.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A male child, aged 1 year, with pulmonary atresia, ventricular septal defect and major aorto-pulmonary collateral arteries (PA, VSD, MAPCA) underwent corrective surgery including MAPCA ligation uneventfully. A few hours after admission to the ICU, severe heart failure, refractory to aggressive cardiac support including epinephrine infusion, became worse. Emergent cardiac catheterization on postoperative day 5 demonstrated the residual MAPCA and its occlusion by coil embolization dramatically resolved heart failure, indicating that the primary cause of this hemodynamic instability was likely excessive left-to-right shunt due to MAPCA. Residual LR shunt should be kept in mind to be a rare but significant cause of postoperative serious heart failure.
Masui. The Japanese journal of anesthesiology 11/2010; 59(11):1441-5.
[Show abstract][Hide abstract] ABSTRACT: Amiodarone is widely used in Europe and the United States for refractory ventricular fibrillation (VF) in various situations, such as VF after myocardial infarction or out-of-hospital cardiac arrest. We report a case of successful treatment with amiodarone of refractory VF immediately after releasing aortic cross-clamp in cardiac surgery. A 66-year-old man suffering from severe aortic stenosis underwent aortic valve replacement (AVR). General anesthesia was induced with propofol and remifentanil, and subsequently AVR was performed under cardiopulmonary bypass. Just after releasing aortic cross-clamp, VF occurred, and it continued despite multiple trials of cardioversion with direct current (DC) shocks of 20 J or 30 J. Furthermore, some DC shocks of 30 J or 50 J after administering lidocaine 60 mg and 0.5 mol x l(-1) magnesium sulfate 20 ml were also ineffective. Then, nifekalant 20 mg was administered and DC shocks of 50 J were repeated intermittently, but VF still persisted. Eventually, VF disappeared after a final DC shock of 50 J with intravenous amiodarone 125 mg. Overall duration of VF was 60 minutes. The patient's trachea was extubated three days after the surgery without any complications. Intravenous amiodarone may be one of the most useful remedies for some types of arrhythmias including persistent VE.
Masui. The Japanese journal of anesthesiology 10/2010; 59(10):1266-70.
[Show abstract][Hide abstract] ABSTRACT: Hypoplastic left heart syndrome (HLHS) with intact atrial septum (IAS) is an extreme type of single ventricle physiology among congenital heart diseases, in which a baby cannot supply oxygenated blood into systemic circulation without alternative pathway. We report the case of the neonate undergoing open balloon atrial septostomy (BAS) and bilateral pulmonary artery banding (PAB) soon after scheduled caesarean sections (C/S). A 35-year-old female was pregnant and fetal echocardiography at 32 weeks revealed one of the twins as HLHS/IAS. Severe hypoxia soon after birth was suspected. Thus, scheduled C/S followed by open BAS was planned. At 36 weeks of gestation, the mother was anesthetized with spinal bupivacaine and the female baby with HLHS/IAS was delivered. After diagnosed definitely by pediatric cardiologists, her trachea was intubated by anesthegiologists and umbilical catheters were placed by neonatologists. Then the baby was transferred to neighboring operating theater for BAS 68 minutes after the birth, while her Sp(O2) was maintained around 75-85% through serial procedures. Open BAS and PAB were performed under general anesthesia without any hemodynamic instability or severe hypoxia. Cooperation among anesthegiologists, neonatologists, pediatric cardiologists, and cardiac surgeons is mandatory in order to successfully complete such a rushed procedure.
Masui. The Japanese journal of anesthesiology 10/2010; 59(10):1308-10.
[Show abstract][Hide abstract] ABSTRACT: We report the perioperative management of a 55-year-old man with chronic renal failure requiring long-term hemodialysis, who underwent laparoscopic adrenalectomy for pheochromocytoma. He was pretreated with doxazosin, a calcium channel blocker and a beta-adrenoceptor antagonist to control blood pressure until surgery. His dry weight increased slowly from 57 kg to 58.5 kg for a month increasing the intravascular volume. Neither did the patient develop pulmonary edema nor congestive heart failure preoperatively. Tumor resection was successfully completed under general anesthesia. Although noraderenaline was required to keep adequate blood pressure during surgery and the first day of intensive care unit stay, there was no adverse event during perioperative period. The increasing intravascular volume before pheochromocytoma surgery in a patient on hemodialysis might make the perioperative management safer, although further study is required to determine the adequate level of increment in the preoperative dry weight.
Masui. The Japanese journal of anesthesiology 08/2010; 59(8):1021-4.
[Show abstract][Hide abstract] ABSTRACT: Hemorrhagic shock followed by resuscitation (HSR) causes oxidative stress, which results in multiple organ damage. The kidney is one of the target organs of HSR-mediated oxidative tissue injury. Heme oxygenase (HO)-1, the rate-limiting enzyme in heme catabolism, is induced by oxidative stress; it protects against oxidative tissue injuries. The aim of the present study was to examine the role of renal HO-1 induction after HSR. Rats were subjected to hemorrhagic shock to achieve a mean arterial pressure of 30 mmHg for 60 min, followed by resuscitation with the shed blood. HSR resulted in a significant increase in functional HO-1 protein in the tubular epithelial cells of the kidney, whereas HSR resulted in only a slight increase in gene expression of tumor necrosis factor (TNF)-alpha and inducible nitric oxide synthase (iNOS), and in protein expression of activated caspase-3 solely in renal cells where HO-1 expression was absent. HSR also resulted in a significant increase in Bcl-2 gene expression. Pretreatment of HSR animals with tin-mesoporphyrin (0.5 micromol/kg), a specific competitive inhibitor of HO activity, resulted in a significant decrease in HO activity and exacerbated tissue inflammation and apoptotic cell death as judged by the marked increase in expression of TNF-alpha and iNOS, and in activated caspase-3-positive cells, and the significant reduction in Bcl-2 expression, respectively. These findings indicate that HO-1 induction is an adaptive response to HSR-induced oxidative stress and is essential for protecting tubular epithelial cells from oxidative damage through its anti-inflammatory and anti-apoptotic properties.
International Journal of Molecular Medicine 07/2010; 26(1):27-32. · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hemorrhagic shock and resuscitation (HSR) induces pulmonary inflammation that leads to acute lung injury. Carbon monoxide (CO), a by-product of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. The aim of this study was to examine the effects of CO inhalation at low concentration on lung injury induced by HSR in rats.
Rats were subjected to HSR by bleeding to achieve mean arterial pressure of 30 mm Hg for 60 minutes followed by resuscitation with shed blood and saline as needed to restore blood pressure. HSR animals were either maintained in room air or were exposed to CO at 250 ppm for 1 hour before and 3 hours after HSR.
HSR caused an increase in the DNA binding activity of nuclear factor-kappaB and activator protein-1 in the lung followed by the up-regulation of pulmonary gene expression of tumor necrosis factor-alpha, inducible nitric oxide synthase, and interleukin (IL)-10. HSR also resulted in an increase in myeloperoxidase activity and wet weight to dry weight ratio in the lung, and more prominent histopathologic changes including congestion, edema, cellular infiltration, and hemorrhage. In contrast, CO inhalation significantly ameliorated these inflammatory events as judged by fewer histologic changes, less up-regulation of inflammatory mediators, and less activation of nuclear factor-kappaB and activator protein-1. Interestingly, the protective effects against lung injury afforded by CO were associated with further increases in mRNA expression of IL-10 in the lung.
These findings suggest that inhaled CO at a low concentration ameliorated HSR-induced lung injury and attenuated inflammatory cascades by up-regulation of anti-inflammatory IL-10.
The Journal of trauma 07/2010; 69(1):185-94. · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thrombotic microangiopathy (TMA) is a rare but potentially lethal complication encountered in solid organ and bone marrow transplant recipients that requires rapid recognition, diagnosis, and initiation of therapy. Several causes have been identified, including viral infections and various medications. We report a case of TMA after living-donor liver transplantation (LDLT). A 60-year-old man underwent LDLT for end-stage liver disease secondary to hepatitis C virus. After 6 months, he required re-transplantation because graft failure was caused by a small-for-size graft. The immunosuppressive regimen for the second transplantation consisted of tacrolimus and prednisolone; cyclosporine (CsA), mycophenolate mofetil, and prednisolone had been used for the first transplantation. Despite multiple transfusions of packed red blood cells and concentrated platelets, his hemoglobin and platelets decreased and lactate dehydrogenase increased following re-transplantation. Hematological evaluation revealed findings consistent with TMA. As soon as TMA was diagnosed, the calcineurin inhibitor (CNI) was changed from tacrolimus to CsA, and fresh frozen plasma (FFP) was given. The patient's platelets gradually increased after the CNI was changed, and no transfusions were needed. Therefore, tacrolimus was suspected as the cause of the patient's TMA. Early diagnosis, switching CNIs, and FFP supplementation allowed the TMA to resolve without the need for plasma exchange.
Journal of Anesthesia 05/2010; 24(4):614-7. · 0.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic pain conditions such as phantom limb pain and complex regional pain syndrome are difficult to treat, and traditional pharmacological treatment and invasive neural block are not always effective. Plasticity in the central nervous system occurs in these conditions and may be associated with pain. Mirror visual feedback therapy aims to restore normal cortical organization and is applied in the treatment of chronic pain conditions. However, not all patients benefit from this treatment. Virtual reality technology is increasingly attracting attention for medical application, including as an analgesic modality. An advanced mirror visual feedback system with virtual reality technology may have increased analgesic efficacy and benefit a wider patient population. In this preliminary work, we developed a virtual reality mirror visual feedback system and applied it to the treatment of complex regional pain syndrome.
A small open-label case series. Five patients with complex regional pain syndrome received virtual reality mirror visual feedback therapy once a week for five to eight sessions on an outpatient basis. Patients were monitored for continued medication use and pain intensity.
Four of the five patients showed >50% reduction in pain intensity. Two of these patients ended their visits to our pain clinic after five sessions.
Our results indicate that virtual reality mirror visual feedback therapy is a promising alternative treatment for complex regional pain syndrome. Further studies are necessary before concluding that analgesia provided from virtual reality mirror visual feedback therapy is the result of reversing maladaptive changes in pain perception.
Pain Medicine 03/2010; 11(4):622-9. · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The progression and interrelationship of mediators that are released, activated or suppressed after major surgery appear to play an important role in responses to surgical stress. Heat shock protein 70 (HSP70) is stress-induced and acts like a cytokine to modulate pro-inflammatory mediators, such as tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS), by stimulating toll-like receptor 4 (TLR4) signaling. We hypothesized that this effect would occur after major surgery, such as esophagectomy. We therefore measured the expression of HSP70, TLR4, TNF-α and iNOS mRNA in peripheral blood mononuclear cells (PBMCs) from 11 patients who underwent esophagectomy with thoracoabdominal procedures at postoperative day (POD) 1 and POD3 using real-time polymerase chain reaction, and compared the results to expression levels in 6 healthy adult volunteers (controls). We also measured plasma cortisol as a well-known stress hormone. The expression of HSP70 mRNA in PBMCs was 2.1-fold higher on POD1 compared to the controls (P=0.041) and was positively correlated with TLR4 mRNA (r2=0.45, P=0.0007). The expression of TNF-α mRNA tended to be lower on POD1 (P=0.055) and was significantly decreased on POD3 (P=0.016), and iNOS mRNA were significantly lower on POD1 (P=0.0015) and POD3 (P=0.0003) compared to the controls. Moreover, there was a positive correlation between the expression of TLR4 mRNA and plasma cortisol levels (r2=0.24, P=0.021). The expression of HSP70 mRNA in PBMCs in the early postoperative period was significantly higher and positively correlated with TLR4 mRNA. This suggests that HSP70-TLR4 signaling has an important role in postoperative inflammatory responses. However, the expression of pro-inflammatory mediators, including TNF-α and iNOS mRNA, was significantly decreased postoperatively. This may be caused by the anti-inflammatory mechanism of cortisol. Our findings indicate that responses to surgical stress reflect simultaneous pro-inflammatory and anti-inflammatory responses, and are complex.
Molecular Medicine Reports 01/2010; 3(5):765-9. · 1.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study aimed to investigate the annual incidence and characteristics of perioperative pulmonary thromboembolism (PTE) in Japan from 2005 through 2007, and to compare the current trend with that observed in our previous studies conducted since 2002.
In the 3-year study period, a questionnaire was annually mailed to every institution certified as a training hospital for anesthesiologists by the Japanese Society of Anesthesiologists (JSA). The survey included the parameters of age, sex, type of surgery, and the risk factors in patients who were operated upon.
The average rate of effective responses was 55.1%, and a total of 825 cases of perioperative PTE were registered in the 3-year study period. The incidence of perioperative PTE was 2.79 per 10,000 cases in 2005, 2.25 per 10,000 cases in 2006, and 2.57 per 10,000 cases in 2007. The incidence of PTE in all the 3 years was significantly lower than that observed in 2002-03 (P < 0.01). In addition, the incidence of fetal PTE in 2006 and 2007 was also significantly lower than that in 2002-03. The incidence of PTE in older persons (66-85 years) was approximately twice (4.70 per 10,000 cases) and that in the oldest persons (> 86 years) was approximately thrice (6.28 per 10,000 cases) the incidence in middle-aged individuals (2.17 per 10,000 cases). PTE was found to be more frequent in females than in males (males, 1.89 per 10,000 cases; females, 3.75 per 10,000 cases). The types of surgery that most commonly resulted in perioperative PTE were limb and/or hip joint surgery (5.57 per 10,000 cases), thoracotomy with laparotomy (5.19 per 10,000 cases), and spinal surgery (4.49 per 10,000 cases). Perioperative PTE was fatal in 185 patients (22.4%), and the mortality rate of patients who had not received prophylaxis was significantly higher (37.8%) than that of patients who received anticoagulant drugs (20.8%). Guidelines for prevention of perioperative PTE were accepted by 58% of all training institutions.
The incidence of perioperative PTE and fetal PTE has currently decreased; however, prophylaxis with anticoagulant drugs may have reduced the mortality in some cases.
Masui. The Japanese journal of anesthesiology 12/2009; 58(12):1567-73.
[Show abstract][Hide abstract] ABSTRACT: Preventing harmful hyperglycemia is important in critical illness. However, insulin therapy increases the risk of hypoglycemia. In patients with diabetes, isomaltulose-based enteral formula (IF) feeding has been shown to reduce glycemia. This randomized controlled crossover study was conducted to determine whether IF feeding improves glycemia in postoperative critically ill patients.
Eight patients who developed hyperglycemia (>150 mg/dL) after esophagectomy were included. Patients were randomized to either the IF or the standard feeding formula (SF) arm. After 16 hours of administration of randomized formula and 8 hours of washout, patients crossed over to the other formula for the next 16 hours. Continuous glucose measurement using STG-22 (Nikkiso, Tokyo, Japan) was performed during the trial.
Maximum blood glucose concentration was 181 mg/dL with IF, significantly lower than the 206 mg/dL with SF (P = .001). Mean glycemia during feeding periods was 162 mg/dL with IF, significantly lower than the 176 mg/dL with SF (P = .0001). Seven (87.5%) patients taking SF exceeded 180 mg/dL compared with 3 (37.5%) patients taking IF (P = .005). This effect was seen without any risk of hypoglycemia and complication.
Isomaltulose-based enteral formula might be useful for safer glycemic control in postoperative critically ill patients. Further study to determine clinical benefit of IF feeding is justified.
Journal of critical care 09/2009; 25(1):90-6. · 2.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In Japan, emergency blood transfusion practices including ABO-compatible, different blood group transfusion and uncross-matched, ABO-identical blood group transfusion are very limited possibly due to adherence to identical blood transfusion as well as fear of hemolytic reactions due to anti-A, anti-B, anti-RhD and unexpected antibodies. Purpose of the study is to examine the incidence of hemolytic reactions due to compatible, ABO-different blood group transfusion.
We conducted a questionnaire survey regarding emergency compatible, different blood group transfusion in the operating theater in hospitals with more than 500 beds among those with an accredited Department of Anesthesiology regarded as regional hospitals. Of 384 institutions, 247 responded to the questionnaire. During the year 2006, compatible, ABO-different blood group transfusion was reported in 112 patients from 32 hospitals, among which 105 patients in 26 hospitals were available for further analysis.
Compatible red cell concentrate (RCC), fresh frozen plasma (FFP), and platelet concentrate (PC) were transfused in 23, 10, and 83 patients, respectively. Total amount of compatible RCC, FFP, and PC were 232, 162, and 1,679 units, respectively. In patients who were transfused with compatible RCC, two patients had unexpected antibodies. Overall mortality rate within the 30th post-operative day was 23%. In 80 patients, in whom only PCs were used as compatible blood products, blood loss was 86 +/- 85 ml x kg(-1), 65% of patients underwent cardiovascular surgery, and mortality was 11%, implying that compatible PC was transfused mainly to avoid hemorrhagic diathesis in cardiovascular patients. In 64 patients with blood type of A, B, or AB, who underwent compatible PC transfusion, type O PC, incompatible blood products, were transfused in 9 patients. In 21 patients, in whom only RCCs were used as compatible blood products, blood loss was 206 +/- 224 ml x kg(-1), and mortality was 57%. Therefore, compatible RCCs were transfused mainly to avoid life-threatening events. Uncross-matched, ABO-identical RCC transfusion was performed only in 29% of patients among these 21 patients. Transfusion-related hemolytic reactions were not reported in all 104 patients available for this analysis.
Although the patient number was small, the finding that there were no hemolytic reactions might promote emergency blood transfusion practices in Japan. High mortality rate and a low rate of uncross-matched, ABO-identical RCC transfusion in patients with compatible RCC transfusion suggest that promoting emergency blood transfusion practices might reduce mortality rate due to massive hemorrhage in the operating theater.
Masui. The Japanese journal of anesthesiology 09/2009; 58(8):1045-54.
[Show abstract][Hide abstract] ABSTRACT: Insulinomas are rare tumors, the incidence of which is 1-2 per million. Patients with insulinomas present with symptoms of hypoglycemia secondary to insulin hypersecretion. Surgical resection is a treatment of choice and offers the only chance of cure. The important points in anesthesia are the precaution against hypoglycemia until tumor resection and the control of rebound hyperglycemia soon after tumor resection. We report the anesthetic management of a 5-year-old patient with insulinoma. Soon after the induction of anesthesia, the continuous glucose monitoring was commenced. Until the tumor resection, 10% glucose infusion was required to avoid hypoglycemia. Then, insulin infusion was continued to maintain blood glucose level around 150 mg x dl(-1). All glucose management was guided with continuous glucose monitoring. This is a first case report to show the feasibility and usefulness of continuous glucose monitoring in management of pediatric insulinoma patients. As the blood glucose was dramatically altered during perioperative period, frequent blood glucose measurements or continuous glucose monitoring is mandatory during perioperative period of insulinoma resection.
Masui. The Japanese journal of anesthesiology 07/2009; 58(6):757-9.
[Show abstract][Hide abstract] ABSTRACT: Validation of a scoring algorithm for non-overt disseminated intravascular coagulation (DIC) proposed by the International Society on Thrombosis and Haemostasis (ISTH) is still incomplete. It was the objective of this study to assess the impact of including AT to non-overt DIC scoring on the predictability for intensive care unit (ICU) death and the later development of overt-DIC defined by the Japanese Ministry of Health and Welfare (JMHW) or the ISTH. We performed a retrospective observational study conducted in 364 patients in critical care. Coagulation parameters obtained daily for DIC screening were utilised for scoring. There were 194 and 196 patients scored as positive non-overt DIC with and without AT, respectively; diagnostic agreement between the two was 78%. As compared with patients without non-overt DIC, these non-overt DIC patients had significantly higher mortality. In 37 ICU non-survivors, positive non-overt DIC scoring with AT preceded ICU death by a median of 6.8 days, which was significantly earlier as compared with a median of 5.4 days for non-overt DIC without AT (p = 0.022). In patients who developed overt-DIC after admission, the time period from positive non-overt DIC to positive overt-DIC was significantly longer when AT was utilised (overt-DIC ISTH; 1.3 days vs. 0.1 days, p = 0.004, overt-DIC JMHW; 2.5 days vs. 2.0 days, p = 0.04, with AT vs. without AT, respectively). Non-overt DIC scoring predicted a high risk of death in critically ill patients. When information on AT levels was included, non-overt DIC scoring was found to predict development of overt-DIC significantly earlier than non-overt DIC scoring without AT.
Thrombosis and Haemostasis 05/2009; 101(4):696-705. · 5.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The incidences of intra-operative critical arrhythmia related to epinephrine under halogenated inhalational anesthesia were analysed according to questionnaire to 1108 JSA (Japanese Society of Anesthesiologists) Certified Training Hospital. The survey details included prospective (from July 16th, 2008 to Aug 15th, 2008) and retrospective (from Jan 1st, 2007 to Dec 31th, 2007) incidences of critical arrhythmia due to epinephrine under halogenated inhalational anesthesia. Among the 1108 institutions, effective responses were obtained from 583 institutions. A total of 1.2 case per 100,000 cases of critical arrhythmia were recorded in the retrospective study, and no case was recorded in the prospective study. The use of epinephrine under halogenated inhalational anesthesia was safe, but careful use is recommended.
Masui. The Japanese journal of anesthesiology 04/2009; 58(3):378-83.
[Show abstract][Hide abstract] ABSTRACT: Lipopolysaccharide (LPS) is one of the major causes of septic shock. The polymyxin B-immobilized filter column (PMX) was developed for the adsorption of endotoxin by direct hemoperfusion and has been used for the treatment of LPS-induced septic shock. In this study, we demonstrated that PMX also specifically bound monocytes from the peripheral blood leukocytes of septic patients by mean of an analysis of bound cells using immunocytochemical and electron microscopic techniques. The specific removal of monocytes from septic patients may produce beneficial effects by reducing the interaction between monocytes and functionally associated cells including vascular endothelial cells.
[Show abstract][Hide abstract] ABSTRACT: Hemorrhagic shock causes oxidative stress that leads to tissue injuries in various organs including the lung, liver, kidney and intestine. Excess amounts of free heme released from destabilized hemoproteins under oxidative conditions might constitute a major threat because it can catalyze the formation of reactive oxygen species. Cells counteract this by rapidly inducing the rate-limiting enzyme in heme breakdown, heme oxygenase-1 (HO-1), which is a low-molecular-weight stress protein. The enzymatic HO-1 reaction removes heme. As such, endogenous HO-1 induction by hemorrhagic shock protects tissues from further degeneration by oxidant stimuli. In addition, prior pharmacological induction of HO-1 ameliorates oxidative tissue injuries induced by hemorrhagic shock. In contrast, the deletion of HO-1 expression, or the chemical inhibition of increased HO activity ablated the beneficial effect of HO-1 induction, and exacerbates tissue damage. Thus, HO-1 constitutes an essential cytoprotective component in hemorrhagic shock-induced oxidative tissue injures. This article reviews recent advances in understanding of the essential role of HO-1 in experimental models of hemorrhagic shock-induced oxidative tissue injuries with emphasis on the role of its induction in tissue defense.
Journal of Clinical Biochemistry and Nutrition 02/2009; 44(1):28-40. · 2.25 Impact Factor