新喋呤与内毒素对烧伤后多器官功能障碍综合征的诊断价值

目的：探讨循环新喋呤与内毒素对严重烧伤后多器官功能障碍综合征（Ｍｕｌｔｉｐｌｅｏｒｇａｎｄｙｓｆｕｎｃｔｉｏｎｓｙｎｄｒｏｍｅ，ＭＯＤＳ）的诊断价值；方法：对４７例烧伤面积（ＴＢＳＡ）大于３０％（３０％～１００％）患者血清新喋呤、血浆内毒素水平的变化进行动态观察。分别计算新喋呤、内毒素、新喋呤合并内毒素诊断多器官功能障碍综合征（ＭＯＤＳ）的敏感性、特异性及准确性等。结果：根据新喋呤、内毒素对ＭＯＤＳ的预警阈值（３５．０ｎｍｏｌ／Ｌ和５００ＥＵ／Ｌ），新喋呤合并内毒素诊断ＭＯＤＳ的敏感性、特异性及准确性分别为８８．３％、９３．７％、９１．６％，均明显高于单独应用新喋呤或内毒素。结论：动态同步观察循环新喋呤和内毒素水平的变化，对于严重烧伤后ＭＯＤＳ的早期诊断与病程监测具有一定的临床价值。     

Increased serum neopterin concentration as indicator of disease severity and poor survival in multiple myeloma

In this study we investigated serum neopterin levels in 73 multiple myeloma (MM) patients (63 determinations at diagnosis, 58 in remission, and 35 at relapse), in 56 monoclonal gammopathies of undetermined significance (MGUS), and in 70 normal controls. Median neopterin level was 5.3 nmol/l in normal controls, 6.8 nmol/l in MGUS, and 10.7 nmol/l in MM patients. In comparison to healthy subjects, significantly higher levels were observed in MM patients (p less than 0.0001). A statistical difference was observed between MGUS and MM patients at diagnosis (p less than 0.007). Compared to diagnosis, a further increase was noticed during relapse, suggesting a correlation between neopterin and disease activity. The prognostic significance of raised neopterin levels was confirmed by a survival analysis. Median survival for patients with high values was 20 months, whereas it was 63.9 months for those with low values (log-rank test p less than 0.003). Serum neopterin concentrations also correlated to beta 2 microglobulin levels and the percentage of CD38+ circulating lymphocytes, indicating a link between neopterin and other myeloma prognostic factors.     

Elevated urinary neopterin: A clue of activated macrophage and cellular immune response in the pathogenesis of idiopathic nephrotic syndrome

Summary: A study of cell mediated immunity (CMI) activation in patients with idiopathic nephrotic syndrome (INS) in the tropics was undertaken. Cell mediated immunity activation was investigated by measuring urinary neopterin excretion. All 31 patients with idiopathic nephrotic syndrome due to either minimal change nephrotic syndrome (MCNS), and focal and segmental glomerulosclerosis (FSGS) had significant elevation of neopterin excretion (mean values 451, 544 μmol neopterin/mol creatinine) when compared with 222 normal subjects (mean value 130, P < 0.001). However, in 25 patients with non-nephrotic IgA nephropathy and eight nephrotic membranous nephropathy the urinary neopterin was not raised (mean value 131 and 129). A further 10 patients with MCNS were restudied when in complete remission and their urinary neopterin was found to have decreased significantly (mean value 186); however, this level was still above the normal range. Our study suggests that CMI and macrophage activation takes place in the pathogenesis of idiopathic nephrosis.     

Interleukin-6 and neopterin in renal transplant recipients: a longitudinal study

Serum and urine interleukin-6 (IL-6) levels and serum neopterin/creatinine ratios were longitudinally studied in 86 renal transplant recipients until 4 months after transplantation. During acute rejection and acute tubular necrosis (ATN), serum and urine IL-6 levels were elevated compared to during stable transplant function (P<0.001). During acute rejection, serum IL-6 levels increased at least 2 days before plasma creatinine started to rise (P<0.05), indicating its early involvement in the rejection process. During cytomegalovirus (CMV) disease, serum, but not urine, IL-6 levels were higher (P<0.01), and serum neopterin/creatinine values were higher than during stable transplant function, ATN, or acute rejection (P<0.01). No significant differences with stable transplant function occurred during cyclosporin A toxicity. Measurement of serum IL-6 provided a sensitivity of 84% and a specificity of 85% for the diagnosis of acute rejection episodes not coinciding with ATN. All cases of CMV disease could be diagnosed by measurement of serum neopterin/creatinine, which provided a specificity of 73%.     

Extensive white matter involvement in hemorrhagic shock and encephalopathy syndrome

Reported is a case of hemorrhagic shock and encephalopathy syndrome (HSE) with extensive white matter involvement. A three year old, previously healthy boy was presented with an acute onset of fever, loss of consciousness and convulsions. He had disseminated intravascular coagulation, metabolic acidosis, non-ketotic hypoglycemia and hepatorenal dysfunction. The computed tomography (CT) scan of his head on the second day of illness demonstrated symmetric, extensive low-density areas in the cerebral and cerebellar white matter. The child died on the 13th hospital day. A post-mortem histopathological examination of the liver revealed centrilobular necrosis and infiltration of fatty acid droplets. The concentrations of serum 2′,5′-oligoadenylate synthetase and urinary neopterin were markedly elevated, indicating excessively activated cell-mediated immunity. This overproduction of inflammatory cytokines might play an important role in the pathogenesis of the brain lesion as well as in other clinical and laboratory manifestations. The patient had a decreased serum level of α1-antitrypsin, which may have been associated with the development of uncontrolled inflammation and coagulation disorder.     

Neopterin and hsCRP are not correlated in gestational diabetes mellitus

Objective: To determine serum neopterin and high sensitive C-reactive protein (hsCRP) levels in patients with and without gestational diabetes mellitus (GDM).

Methods: Neopterin and hsCRP levels were quantified in 28 women with GDM and 20 pregnant women with normal glucose tolerance (NGT). Postpartum neopterin and hsCRP levels were measured in a follow-up study.

Results: Neopterin levels were significantly higher in women with GDM than in women with NGT (15.89?±?8.19?nmol/L versus 10.4?±?3.8?nmol/L, p?p?p?=?0.9, respectively). In contrast, hsCRP levels decreased after delivery in patients with GDM (5.74?±?3.91 versus 3.78?±?2.78, p?r?=?0.3, p?=?0.02) and fasting glucose (r?=?0.4, p?=?0.004), postprandial glucose (r?=?0.3, p?=?0.01), HbA1c (r?=?0.3, p?=?0.02), whereas hsCRP levels were correlated with pre-pregnancy (r?=?0.3, p?=?0.04) and pregnancy body mass index (r?=?0.4, p?=?0.008). No correlation between serum neopterin and hsCRP levels was found (p?=?0.9).

Conclusion: Neopterin levels increased in patients with GDM; hence, it may be related to inflammation. However, the lack of correlation between neopterin and hsCRP suggests the role of different attitudes of these two parameters in the course of pregnancy and GDM.     

银屑病患者血清中新蝶呤的水平和意义

目的：探讨新蝶呤（neopterin，Npt）在银屑病血清中的水平及其意义。方法：检测37例寻常型银屑病患者不同时期及治疗前后血清Npt水平。结果：银屑病患者血清Npt水平较健康对照组显著升高（P=0．001），血清Npt水平进行期较静止期增高（P〈0．05），治疗后，明显下降（P=0．001）。银屑病患者治疗前、后血清Npt水平与PASI评分有显著正相关（P=0．01，r=0．61；P=0．01，r=0．66）。结论：血清Npt可能在银屑病的发病机制中起着重要作用，并与疾病的活动和严重程度密切相关．     

Homocysteine-lowering therapy does not affect inflammatory markers of atherosclerosis in patients with stable coronary artery disease

OBJECTIVES: A high level of total homocysteine (tHcy) is a risk marker for cardiovascular disease (CVD), and is related to inflammation. We wanted to test the effect of homocysteine-lowering B-vitamin therapy, as used in the Western Norway B-vitamin Intervention Trial (WENBIT), on inflammatory markers associated with atherosclerosis. DESIGN: Single centre, prospective double-blind clinical interventional study, randomised in a 2 x 2 factorial design. SUBJECTS AND METHODS: Ninety patients (21 female) with suspected coronary artery disease (CAD), aged 38-80 years, were blindly randomised into one of four groups of daily oral treatment with (A) folic acid (0.8 mg)/vitamin B12 (0.4 mg)/vitamin B6 (40 mg), (B) folic acid/vitamin B12, (C) vitamin B6 alone or (D) placebo. Blood samples were collected before and after 6 months of treatment. RESULTS: Before intervention, median levels of the analytes were: tHcy 11.0 micromol L(-1), neopterin 8.1 nmol L(-1), soluble CD40 ligand (sCD40L) 3.9 ng mL(-1), interleukin (IL)-6 1.9 pg mL(-1), C-reactive protein (CRP) 1.9 mg L(-1) and low-density lipoprotein (LDL) cholesterol 3.3 mmol L(-1). tHcy was significantly associated with neopterin (r = 0.49, P < 0.001) and with IL-6 (r = 0.29, P = 0.01), but not with CRP or sCD40L. Neither treatment with folic acid/B12 nor with B6 induced significant changes in any of these inflammatory biomarkers (P >or= 0.14). In patients receiving folic acid/B12 (groups A and B), tHcy was reduced with 33% (P < 0.001). CONCLUSIONS: In patients with stable CAD, homocysteine-lowering therapy with B-vitamins does not affect levels of inflammatory markers associated with atherogenesis. Failure to reverse inflammatory processes, may partly explain the negative results in clinical secondary B-vitamin intervention trials.     

Diagnostic value of neopterin during neutropenic fever and determination of disease activity in childhood leukemias

Neopterin, a pteridine group compound that is secreted from macrophages is shown to be increased in adult leukemia; however there are few studies in childhood leukemia. This study aimed to investigate neopterin levels during childhood leukemia treatment and neutropenic fever episodes for the possibility of using as a marker for disease activity and differentiation of infections. A total of 44 children with acute leukemia, 19 children with infection (control group 1) and 21 healthy children (control group 2) were studied. Median serum neopterin level before induction chemotherapy (day 0) in 25 children (patient group 1) was significantly higher (27.7 nmol/L) than those at the beginning of 30 febrile episodes in 19 children in bone marrow remission (2.2 nmol/L) (patient group 2) and in control group 2 (0.4 nmol/L) (p< 0.05). It was (27.7 nmol/L) also significantly higher in control group 1 than in patient group 2 and control group 2 (p< 0.05). Serum neopterin levels at day 15 (2.1 mmol/L) and day 33 (0.4 mmol/L) of induction were significantly lower than day 0 of ALL subgroup at patient group 1. There were no significant difference in neopterin levels between days 0, 3 and 5 of neutropenic fever as well as between patients with microbiologically and/or clinically documented infections and those with fever of unknown origin in patient group 2 (p> 0.05). Serum neopterin did not show significant correlation with absolute neutrophil count and absolute monocyte count (p> 0.05). In conclusion, elevated neopterin at diagnosis of leukemia with decrement during induction therapy suggest that it might be an indicator of leukemic process; however larger studies for its role in identifying infections are warranted.