磁敏感加权成像测量脑铁含量在帕金森病中的应用研究

目的 应用磁敏感加权成像技术(SWI)半定量分析帕金森病(PD)患者脑灰质核团铁含量的变化、探讨其在PD临床研究中的应用价值.方法 对40例PD患者(Honcn-Yahr分级为Ⅰ级10例、Ⅱ级9例、Ⅲ级9例、Ⅳ级6例、Ⅴ级6例)、33例性别年龄相匹配的正常对照者在3.0T磁共振成像系统上行常规头颅磁共振成像后行磁敏感加权成像,经SWI后处理软件得到相位图像,然后在图像上手工绘制感兴趣区,分别测量黑质致密带、黑质网状带、红核、壳核、苍白球、尾状核头的信号值.结果 PD组与正常对照组相比,黑质致密带、黑质网状带、红核、壳核、苍白球、尾状核头的信号值差异有统计学意义(P值分别为0.002、0.043、0.003、0.023、0.001、0.033).PD组受累更严重侧与正常对照组相比这种差异更明显.PD组黑质致密带和苍白球信号值与Hoehn Yahr分级呈显著负相关,差异有统计学意义(黑质致密带r=-0.943、苍白球r=-0.923.均P＜0.01).黑质网状带、红核、壳核、尾状核头与Hoehn-Yahr分级相关性较小(黑质网状带r=-0.496、红核r=-0.480、壳核r=-0.494、尾状核头r=-0.471.均P＜0.01).结论 利用SWI测定黑质致密带、苍白球的铁含量在PD诊断中具有临床应用价值,并与Hoehn-Yahr分级有良好的相关性,能够反映PD病情严重程度.     

Blood pressure measurement in haemodialysis patients

Several studies suggest that the 24 hour ambulatory blood pressure monitoring (ABPM) predicts left ventricular hypertrophy more accurately than conventional blood pressure measurement (CBPM) with mercury sphygmomanometer. We estimated the left ventricular mass by M-mode echocardiography in 58 patients on regular haemodialysis treatment during the midweek haemodialysis (HD) interval. ABPM was recorded during the 24 hours preceding the dialysis session and the average of values were compared with the average of the 13 pre HD CBPM recorded by nurses during the month preceding the echocardiography study. The two types of BP measurements correlated significantly with each other, (systolic BP r=0.62; p < 0.001 and diastolic BP r=0.74; p < 0.001). The correlation of left ventricular mass with pre-HD systolic BP was stronger (r=0.54; p < 0.001) than with 24h-systolic BP (r=0.33; p<0.01). The overall accuracy of prediction was also similar (68% for pre HD-CBPM; 67% for 24h-ABPM). Measurements of diastolic BP did not correlate significantly with LVM. Our data suggest that 24h-ABPM does not offer any advantage over pre HD-CBPM in predicting left ventricular hypertrophy in HD patients     

Age-related iron deposition in the basal ganglia of controls and Alzheimer disease patients quantified using susceptibility weighted imaging

This study aimed to investigate age-related iron deposition changes in healthy subjects and Alzheimer disease patients using susceptibility weighted imaging. The study recruited 182 people, including 143 healthy volunteers and 39 Alzheimer disease patients. All underwent conventional magnetic resonance imaging and susceptibility weighted imaging sequences. The groups were divided according to age. Phase images were used to investigate iron deposition in the bilateral head of the caudate nucleus, globus pallidus and putamen, and the angle radian value was calculated. We hypothesized that age-related iron deposition changes may be different between Alzheimer disease patients and controls of the same age, and that susceptibility weighted imaging would be a more sensitive method of iron deposition quantification. The results revealed that iron deposition in the globus pallidus increased with age, up to 40 years. In the head of the caudate nucleus, iron deposition peaked at 60 years. There was a general increasing trend with age in the putamen, up to 50–70 years old. There was significant difference between the control and Alzheimer disease groups in the bilateral globus pallidus in both the 60–70 and 70–80 year old group comparisons. In conclusion, iron deposition increased with age in the globus pallidus, the head of the caudate nucleus and putamen, reaching a plateau at different ages. Furthermore, comparisons between the control and Alzheimer disease group revealed that iron deposition changes were more easily detected in the globus pallidus.     

Factors influencing iron requirements in haemodialysis patients

It is well known that haemodialysis patients are prone to developing iron deficiency. Our study looks for data to establish the factors influencing the varying iron needs among these patients.     

Quantitative measurement of iron stores with diethylenetriamine penta-acetic acid

The use of the chelating agent diethylenetriamine penta-acetic acid (DTPA) for measuring body storage iron was investigated in patients with iron excess whose stores could be determined by venesection.Iron excretion after DTPA bore a close semi-logarithmic relationship to body iron stores when these were increased. The excretion of DTPA-bound (59)Fe was similarly related to the size of the stores, indicating that the increased iron excretion produced by DTPA in iron overload states reflects both increased tissue iron available for chelation and greater stability of the iron-chelate complex. Evidence was obtained that injected (59)Fe-DTPA could be used as a marker for chelated tissue iron enabling the DTPA-chelatable body iron pool to be calculated.There was a highly significant correlation between DTPA-chelatable iron and body storage iron. The regression intercept approximated to the origin, implying a specific relation between the DTPA effect and storage iron. The SE of the mean estimate for storage iron on DTPA-chelatable iron was 0.25 g (5.6%).Mean storage iron values of 392 mg for males and 243 mg for females were predicted from the findings in control subjects.     

磁敏感加权成像检测脑内铁沉积在老年认知障碍中的应用价值

目的 应用磁敏感加权成像（SWI）分析老年人轻度认知功能障碍（MCI）和阿尔茨海默病（AD）患者脑内铁沉积的特点及其与简易精神状态检查量表（MMSE）评分变化的相关性,评估脑内铁含量增加在预测MCI向AD转化中的价值。方法 选取2009年11月至2013年1月入院于上海交通大学附属上海市第六人民医院老年科的MCI患者22例,AD患者20例及认知功能正常的老年人18例,行常规磁共振成像（MRI）及颅脑SWI检查,使用校正相位图计算出相应的角弧度值,量化海马与尾状核头的铁沉积。采用方差分析进行组间比较;角弧度值与MMSE评分的相关性分析采用Pearson相关性分析方法。MCI组患者随访1年,根据再次MMSE评分结果分为AD转化组和非AD转化组。比较随访前后两组间角弧度值的变化量有无差异。结果 MCI组左侧海马、左侧尾状核头的角弧度值与对照组比较,差异有统计学意义（P＜0.05）;AD组双侧海马、左侧尾状核头的角弧度值与对照组比较,差异有统计学意义（P＜0.05）。双侧海马角弧度值与MMSE评分相关。随访1年后,MCI组22例患者中有5例进展为AD（22.7%）,进展为AD的5例患者较稳定于MCI组的17例患者左侧海马角弧度值增加更多（P＜0.05）。结论 脑内局灶性铁沉积增加与认知功能减退有关;左侧海马铁沉积的异常增加可能是预测MCI向AD进展的敏感指标。     

MRI of hepatic iron deposition in patients with renal transplant

Excess hepatic iron deposition was found in five of 15 (33%) renal transplant patients undergoing magnetic resonance (MR) screening for avascular necrosis of the femoral heads. Only one of these patients had overt liver disease. The number of prior blood transfusions was a significant factor for this deposition, whereas the age and sex of the patients, number and type of transplants, histocompatibility alleles (HLA), and years of hemodialysis and of chronic renal failure were not significant etiological factors. Liver/fat intensity ratios of less than 0.29 on T1-weighted images and ratios of less than 0.21 on T2-weighted images and a calculated T2 value of less than 35 ms were the best indicators of iron overload. Renal transplant patients are at great risk for excess hepatic iron deposition and MR imaging is a promising tool for the diagnosis of iron overload in this patient population.     

Total dose infusion of intravenous iron in patients with chronic kidney disease receiving haemodialysis

A regimen of a single high dose iron administration was initially adopted for patients commencing haemodialysis (HD) treatment. Iron stores are established and iron metabolism and erythropoiesis stabilise allowing haematinic parameters to be more confidently assessed for use in anaemia management decisions. High doses of IV iron delay the need for subsequent iron supplementation. A high-dose, low-frequency iron infusion regimen for all HD patients was adopted. The outcomes of administering this dosage regimen are reported as observational retrospective analysis using patient record data in 2009. Patients received three [median; semi-interquartile range (SIQR) 0.5] high-dose iron infusions during the year. The median infusion dose was 1100 mg iron (SIQR 0.0) and the median amount of iron received during the year by each patient was 3200 mg (SIQR 750). The median haemoglobin (Hb) level prior to infusion was 108 g/l and post infusion 114 g/l; ZHb = 2.656, p = 0.008). Ferritin levels increased from a median of 376 μg/l preinfusion to 690 μg/l postinfusion; Zferritin =-4.796, p < 0.001. The median time between infusions was 125 days (approximately four months). The 51 patients (76%) who received three or less infusions within the study period received 2537 mg (mean) of iron. These findings indicate that both Hb and ferritin levels can be adequately managed using a high-dose, low-frequency regimen of IV iron in patients undergoing HD.     

Usefulness of measuring reticulocyte hemoglobin equivalent in the management of haemodialysis patients with iron deficiency

The evaluation of iron status in dialysis patients provides information essential to the planning of adequate recombinant human erythropoietin treatment. The cellular iron status of the patients can be determined from the recently available measurement of reticulocyte hemoglobin equivalent (RET-He). RET-He is measured on the basis of automated fluorescent flow cytometry which in the reticulocyte channel, using a polymethine dye, also measures the mean value of the forward light scatter intensity of mature red blood cells and reticulocytes. These values equate with reticulocyte hemoglobin content. In this study, to clarify the accuracy of RET-He in diagnosing iron deficiency in dialysis patients, we initially compared RET-He with such iron parameters as serum ferritin levels, transferrin saturation and content of reticulocyte hemoglobin (CHr) which has been established as indicators of functional iron deficiency. Secondly, we investigated the changes in RET-He during iron supplementation for iron-deficient patients to determine whether this marker is a prospective and reliable indicator of iron sufficiency. The participants in this study were 217 haemodialysis patients. Iron deficiency was defined as havsing a transferrin saturation (TSAT) < 20% or serum ferritin < 100 ng/ml. Conventional parameters of red blood cells and RET-He were measured by on a XE-2100 automated blood cell counter (Sysmex). CHr was measured on an ADVIA120 autoanalyser (Siemens). RET-He mean value was 32.4 pg and good correlation (r = 0.858) between RET-He and CHr is obtained in dialysis patients. Receiver operating characteristic curve analysis revealed, values of the area was 0.776 and at a cutoff value of 33.0 pg, a sensitivity of 74.3% and a specificity of 64.9%, were achieved. Iron supplements given to the patients with low TSAT or ferritin, RET-He responded within 2 weeks, and this seemed to be a potential advantage of using RET-He in the estimation of iron status. RET-He is a new parameter, equivalent value to CHr, and is easily measurable on the widely spread and popular blood cell counter and is a sensitive and specific marker of iron status in dialysis patients.     

Echocardiographic abnormalities in patients with transfusion-dependent anemia and secondary myocardial iron deposition

The heart was evaluated by echocardiography in 56 patients at risk for myocardial iron deposition. Fifty-four had congenital anemia for which they required repeated transfusions, and two had primary hemochromatosis. The data, plotted according to one of three functions of the body surface area, were compared to values obtained in 105 normal subjects whose age spanned a similar range. Left ventricular wall thickness, transverse dimension and mass, as well as left atrial transverse dimension, were increased in the majority of patients with chronic iron overload despite the infrequent occurrence of cardiac enlargement on routine chest films (32 per cent) or electrocardiographic abnormality (16 per cent). Left ventricular ejection fraction was normal in all but four patients. These four patients died within a six month follow-up period suggesting that deterioration in systolic function is an indicator of poor prognosis. Our findings indicate that echocardiography provides a simple noninvasive means for assessing changes in cardiac structure and function that should prove useful in the serial evaluation of patients who are at risk for the development of myocardial iron deposition.     

Functional mapping of disease susceptibility loci using cell biology

In most genome-wide linkage studies, implication of a causative disease gene often requires years of expanding the study to more families and finer mapping of the initially described region. Even after such efforts, unobtainable sample sizes can be required to make statistically meaningful conclusions about a single gene. Here we demonstrate that by adding a layer of functional biology to statistical genetic results, this process can be accelerated. The diabetes susceptibility locus (chromosome 18p11) was systematically dissected by using a cell-based secretion assay and RNA interference, and we identified laminin alpha1 to have a role in pancreatic beta cell secretion. The screen was extended to identify laminin receptor 1 as a functional partner in regards to beta cell function. Our approach can potentially be widely used in the setting of high-throughput cellular screening of other loci to identify candidate genes.     

Clinical significance of hepatic iron deposition and serum iron values in patients with chronic hepatitis C infection

OBJECTIVES: To assess the potential association between hepatic iron deposition or serum iron values and hepatic fibrosis and inflammatory activity in patients with chronic hepatitis C virus infection. METHODS: In 100 consecutive patients with hepatitis C virus infection, tissue iron deposition was assessed by quantifying iron stain on liver biopsy specimens. Serum iron, ferritin, and transferrin saturation were determined by standard laboratory procedures. Statistical analyses incorporated potential confounders associated with hepatic fibrosis. RESULTS: Twenty-one patients had no fibrosis (stage 0), 13 had portal fibrosis (stage 1), 31 had periportal fibrosis (stage II), 10 had bridging fibrosis (stage III), and 25 had cirrhosis (stage IV). Positive iron stain found in liver biopsy specimens of 19 patients was associated with stage III or IV fibrosis (p = 0.004). No significant difference was found between the iron concentration or the hepatic iron index in patients with stage III or IV fibrosis compared with patients with stage I or II fibrosis. At least 1 of 3 serum iron values assessed was abnormal in 55 patients. In univariate analysis, elevated serum iron (p = 0.01), serum ferritin (p < 0.001), and transferrin saturation (p = 0.002) were associated with stage III or IV fibrosis. In multivariate analysis, the only independent predictive factor of severe hepatic fibrosis was serum ferritin (p < 0.02; odds ratio = 11.35). The serum ferritin value and tissue iron stain had a significant positive correlation (p < 0.001). CONCLUSIONS: Increased hepatic iron deposition may be associated with more advanced hepatic fibrosis in patients with chronic hepatitis C virus infection. The serum ferritin value, an independent predictor of severe hepatic fibrosis in patients with chronic hepatitis C virus infection, may predict hepatic iron deposition and severity of fibrosis.     

脑铁沉积与衰老关系的研究进展

铁是人类机体内重要的微量元素,具有重要的生理功能。铁的生理代谢受到机体精密地调节。当大脑内铁稳态发生失衡,出现铁的异常沉积,可导致细胞损伤,而这一过程与机体的衰老密切相关。本文简要总结了机体内铁稳态的调节机制及其与生命体的衰老和预期寿命的联系,阐述了脑铁沉积与衰老之间的密切关系,同时回顾了脑铁沉积测定方法以及去铁治疗的最新研究进展。希望这篇综述可以为铁代谢和衰老相关神经系统疾病的研究提供参考。     

Computerized measurement of iron in liver biopsies: a comparison with biochemical iron measurement

The measurement of stainable hepatic iron using a microcomputer image analysis system was compared with standard biochemical measurements of liver iron content in 103 liver biopsy specimens--29 of idiopathic hemochromatosis, 51 of alcoholic liver disease and 23 of various nonalcoholic liver diseases. Sections were stained using Perls' method for iron; the mean area staining positively for iron was measured and expressed as a percentage of the area of biopsy measured. Biochemical (biochemical hepatic iron [mumol/gm dry wt]/age) and morphometrical (morphometrical hepatic iron [%]/age x 100) hepatic iron indices were calculated. Patients in the idiopathic hemochromatosis group had significantly higher biochemical hepatic iron concentrations (p less than 0.001) compared with the alcoholic liver disease and nonalcoholic liver disease groups: 284 (range = 119 to 631), 21 (range = 2 to 65) and 15 (range = 3 to 31) mumol/gm dry wt, respectively. The biochemical hepatic iron index was also significantly higher (p less than 0.001) in the hemochromatosis group compared with the alcoholic liver disease and nonalcoholic liver disease groups: 5.8 (range = 2.1 to 13.7), 0.4 (range = 0 to 1.6) and 0.4 (range = 0 to 1.1), respectively. Computerized measurements were significantly higher in the hemochromatosis group (p less than 0.001) compared with the alcoholic liver disease and nonalcoholic liver disease groups: 9.72% (range = 1.50% to 29.26%), 0.13% (range = 0% to 1.20%) and 0.03% (range = 0% to 0.40%), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Validation of the measurement of haemodialysis access flow using a haemoglobin dilution test

Monitoring of blood flows in arteriovenous fistulae and arteriovenous grafts is recommended to predict access thrombosis. The ultrasound dilution technique (UDT) is the gold standard. We compare a recently described haemoglobin dilution technique (HDT) with the UDT in measurement of vascular access flow. Access blood flow was measured in 67 stable dialysis patients using HDT by bedside Hemocue (Hemocue AB, ?ngelholm, Sweden) and laboratory measurement. Access blood flow was then measured by UDT in the same dialysis session. Median flow rate by UDT was 950 ml/min (IQR 490-1,440 ml/min), by Hemocue HDT 935 ml/min (IQR 475-1,395 ml/min, p = 0.534), and by laboratory haemoglobin HDT 920 ml/min (IQR 463-1,378 ml/min). Bland-Altman plots demonstrated poor agreement between UDT and HDT (limits of agreement for Hemocue HDT -22.7 to 20.1%, for laboratory HDT -21.2 to 20.4%). HDT can be used to measure vascular access flow but requires validation against clinical outcomes before being recommended as an alternative to UDT.