Variants of RhD – current testing and clinical consequences

Anti‐D (‐RH1) of the Rh blood group system is clinically important as it causes haemolytic transfusion reactions and haemolytic disease of the fetus and newborn. Although most people are either D+ or D−, there is a plethora of D variants, often categorized as either weak D or partial D. These two types are inadequately defined and the dichotomy is potentially misleading. DVI is the D variant most commonly associated with anti‐D production and UK guidelines recommend that patients are tested with anti‐D reagents that do not react with DVI. Weak D types 1, 2, and 3 are seldom, if ever, associated with alloanti‐D production, so a policy recommendation would be to treat patients with those D variants as D+, to preserve D− stocks, whereas patients with all other D variants would be treated as D−. All donors with D variant red cells, including DVI, should be treated as D+.     

上海地区人群维生素D状态研究

目的调查居住在上海地区人群的维生素D状态,探索和建立维生素D"正常"与"适宜"状态测定参考值,为骨质疏松症的防治提供依据。方法 2008年10月至2009年4月、2009年10月至2010年4月用自动电子发光免疫法对在上海地区居住超过5年的2607名健康成人进行血清25羟化维生素D(250HD)和甲状旁腺素(17TH)检测。选择250HD≤12、≤15、≤20和≤30 ng/mL等不同测定值计算低维生素D状态。结果 2607名受试者年龄20～102岁,平均年龄(60.4±20.9)岁,其中男性1150名(44.42%),女性1449名(55.58%),血清250HD平均值为(17.96±6.43)ng/mL,PTH为(2.14±17.10)pg/mL,呈近似正态分布。应用血清250HD4个测定值评估低维生素D状态结果显示:维生素D缺乏或不足的发生率分别为20.85%、32.45%、66.12%和97.36%,15 ng/mL测定值组有明显的增龄性低维生素D状态。2008年10月至2009年4月和2009年10月至2010年4月测定的血清250HD平均值差异有统计学意义。结论结合上海地区人群总体健康水平,维生素D"适宜"状态测定值宜采用20～30 ng/mL,低维生素D状态测定值宜采用15 ng/mL,低维生素D状态的流行率为32.45%。     

Vitamin D: And its role in breast cancer

Vitamin D is a fat soluble vitamin that plays a role in calcium and phosphorus homeostasis. Recently, extensive research on its extraskeletal actions has linked vitamin D deficiency to an increased risk of infection, diabetes mellitus types 1 and 2, cardiovascular disease, obesity, asthma, inflammatory bowel disease, colon, breast, prostate and ovarian cancer and some neurological diseases. There are various mechanisms by which vitamin D influences the natural history of cancer. These include the role of vitamin D in the induction of apoptosis, stimulation of cell differentiation, anti-inflammatory and antiproliferative effects and inhibition of angiogenesis, invasion and metastasis. The aim of this review is to clarify the true role of vitamin D in the onset of breast cancer and evolution of the disease after treatment. A further aim is to suggest new research directions to identify indications and requirements for vitamin D supplementation in patients with breast cancer.     

Vitamin D Nutrition and Bone Disease in Adults

The consequences of vitamin D deficiency upon the skeleton are well known and management in the absence of renal failure is relatively straightforward. Vitamin D, either by mouth or parenterally will correct the deficiency and heal the osteomalacia. The mechanisms underlying the causation of vitamin D deficiency are now better understood and indicate the importance of underlying calcium malabsorption and secondary hyperparathyroidism leading to 1,25(OH)2D-induced catabolism of 25(OH)D and possibly also of vitamin D itself. In such situations, e.g., gastrointestinal and pancreaticobiliary disease, calcium supplementation in addition to vitamin D is indicated. The reasons behind nutritional vitamin D deficiency and the possible role of meat in protecting from osteomalacia await further elucidation, but from epidemiological studies, calcium deficiency, per se, is not implicated in the etiopathogenesis. The concept of vitamin D insufficiency is poorly understood, and difficult to define since a single value or close range of serum 25(OH)D values is unlikely to predict the needs of all subjects. Oral calcium intake and renal function are also likely to be relevant to the level of 25(OH)D which is found to be sufficient or insufficient for any given individual to maintain a normal serum calcium level without secondary hyperparathyroidism. There is increasing evidence that vitamin D insufficiency, by leading to sustained hyperparathyroidism, is prejudicial to the skeleton, particularly cortical bone. Since it is without symptoms until fractures occur, it should be actively sought in those clinical situations now recognized as contributing to risk. It can only be identified by the periodic measurement of serum 25(OH)D and the calcitropic hormones PTH and 1,25(OH)2D. In addition, BMD should be measured in a predominantly cortical site such as the proximal forearm, as well as the more conventional sites of spine and hip. The implications of these recommendations are an increase in the use of assays for PTH and vitamin D metabolites in the groups of subjects discussed in this review. Patients with chronic malabsorption states might reasonably be expected to have measurements performed twice-yearly. When vitamin D insufficiency is found, treatment with either vitamin D, calcium or both will be necessary, depending on the etiology of the insufficiency state in the inividual. In some malabsorptive states, calcium malabsorption is the cause of hyperparathyroidism and oral calcium alone can be used to reverse excess PTH activity in those with an adequate state of vitamin D nutrition. However, even in those vitamin D replete individuals, vitamin D catabolism will be enhanced and a small additional oral dose of vitamin D can do no harm. Regular monitoring of PTH and vitamin D metabolites will remain a necessity to ensure continued efficacy of treatment. Current recommendations for dietary supplements of vitamin D are clearly inadequate [61]. There is compelling evidence for supplements of 800 IU per day in the elderly and other high risk populations. Such a dose is safe and without side effects. The available evidence suggests that this should be combined with calcium supplements of 1200 mg/day [19] and that the current UK recommendations for a daily calcium intake of 700 mg contrast with those from the USA at 1,200 mg for people over 50 years old. Physicians need to be aware of both the small but important problem of vitamin D depletion and osteomalacia with its sometimes ambiguous presentation, and the more common but covert vitamin D (and calcium) insufficiency with its widespread and varied clinical associations.     

Is Bioavailable Vitamin D Better Than Total Vitamin D to Evaluate Vitamin D Status in Obese Children?

Objective:Free hormones are biologically more active in target tissues. Thus, measurement of vitamin D taking into account bioavailability and free vitamin D may be preferable, especially when evidence is contradictory, as in obese children. In order to assess bioavailablity and free vitamin D, using a previously reported formula, vitamin D-binding protein (VDBP) level was measured and VDBP polymorphisms were also evaluated because of variations in binding affinity.Methods:Eighty-four obese and 78 healthy children were included. Anthropometry, calcium, phosphorus, alkaline-phosphatase, parathyroid hormone (PTH), 25 hydroxyvitamin D [25(OH)D], bioavailable-free vitamin D, and VDBP concentration and polymorphism were evaluated in the whole group.Results:Obese girls had significantly higher PTH than normal weight girls (p=0.001). Regardless of gender, obese children had significantly higher concentrations of VDBP (p=0.008) and PTH (p=0.002). When samples taken in winter were analyzed, PTH and VDBP were found to be higher and bioavailable and free vitamin D lower in the obese group. There was no difference in terms of total vitamin D between groups during the winter season.Conclusion:While total, free, and bioavailable vitamin D in the obese group was similar to the control group in autumn, free and bioavailable vitamin D in the winter was lower in the obese than the control group. In addition, PTH was higher in the obese group in both autumn and winter. Therefore, more research is needed to evaluate the variability of free and bioavailable vitamin D according to body habitus, season and the effect any differences may have.     

Detection of weak D and D(VI) red cells in D-negative mixtures by flow cytometry: implications for feto-maternal haemorrhage quantification and D typing policies for newborns

Quantitation of feto-maternal haemorrhage (FMH) by flow cytometry (FC) has been shown to be more accurate than the Kleihauer-Bekte test. Fetal cells will be predominately of R1r or R2r phenotype, with antigen site numbers per cell (SPC) of between 9900 and 16000. If the fetus is of weak D or partial D(VI) phenotype, fewer SPC will be present. Red cells from 20 adult weak D samples were mixed with rr red cells to give 1% mixes. Mixtures were stained and analysed by FC, using two different monoclonal reagents. The SPC of each sample was measured using SOL-ELSA with Scatchard plot analysis. 18 samples could not be distinguished and had <1000 SPC. Two samples that could be distinguished had 1350 and 3000 SPC. Red cells from seven samples of D(VI) were also analysed. None of these samples could be distinguished: SPC were all <1000. Although one of the reagents used reacts with D(VI) cells, quantitation of a D(VI) FMH would not be possible due to low SPC. The ability of fetal red cells with low Rh D SPC to cause immunization is questionable; failure to measure FMH in these cases is unlikely to cause clinical problems, as long as suitably sensitive serological reagents and techniques are used to type all weak D and D variant babies as Rh D positive, and thus ensure that the mother is given the appropriate dose of anti-D.     

维生素D缺乏与非骨骼疾病关系的研究进展

近年来的研究发现,维生素D不仅在骨骼疾病中发挥重要作用,在非骨骼疾病中也具有非常重要的作用。基础研究证实,维生素D受体广泛分布于体内各种组织细胞;临床研究发现,补充维生素D对预防和治疗代谢综合征及心血管疾病、自身免疫性疾病以及肿瘤有重要作用。本文就维生素D缺乏与上述疾病关系的研究进展进行综述。     

维生素D与高血压关系的研究进展

维生素D缺乏在世界范围内非常普遍,目前研究显示维生素D同多种疾病密切相关。维生素D通过作用于维生素D受体发挥作用。近年来,国内外大量研究显示维生素D缺乏同高血压病、冠状动脉疾病、心衰以及心血管不良事件相关,其中维生素D与高血压的研究涉及多个方面,但其具体机制尚不十分清楚。本文将对维生素D与高血压的关系进行综述。     

A high prevalence of hypovitaminosis D in Finnish medical in- and outpatients

OBJECTIVE: To study the prevalence of hypovitaminosis D [serum 25(OH)D < or = 37 nmol L-1)] in Finnish medical in- and outpatients in a cross-sectional study. METHODS: The subjects were 106 consecutive medical inpatients (57 females, 49 males with mean ages of 65 and 58 years) from the Peijas Hospital, Vantaa, Finland, and 99 ambulatory patients (48 females, 51 males with mean ages of 42 and 46 years) contacting a private outpatient centre in Helsinki, Finland. Serum 25(OH)D, vitamin D binding protein (DBP), free vitamin D index (FDI), intact PTH (iPTH), and albumin-corrected calcium were measured. RESULTS: Serum 25-hydroxyvitamin D [25(OH)D] was 37 nmol L(-1) or less in 70% of female and in 61% of male inpatients and in 44% of female and in 37% of male outpatients. In the whole population, a statistically significant inverse association (P < 0.0001) was detected between iPTH and 25(OH)D levels; the iPTH concentration appeared to start increasing when 25(OH)D concentration was 50 nmol L(-1) or less. The association remained the same (P < 0.0001) when FDI was used instead of 25(OH)D in the calculations. When the sexes were analysed separately, the statistically significant association was found only in females (P < 0.0001 for iPTH versus 25(OH)D; P < 0.0001 for iPTH versus FDI) but not in males. CONCLUSION: Hypovitaminosis D is very common amongst Finnish in- and outpatients in both sexes, causing secondary hyperparathyroidism in females. More extensive studies are warranted to elucidate the vitamin D status of the Finnish population.     

Non-classical effects of vitamin D: Non-bone effects of vitamin D

Our understanding of vitamin D has improved considerably in recent years. The role of vitamin D in preventing osteoporotic fractures is now well-established. However, an important controversy has emerged in the last decade concerning the effects of the active form of vitamin D (1,25-dihydroxy-vitamin D) on tissues other than bone (non-classical effects). The demonstration that the vitamin D receptor (VDR) is ubiquitously, expressed combined with increasing observational data supporting a relationship between the level of 25-hydroxy-vitamin D in the serum and chronic metabolic disorders, cardiovascular disease and neoplasms, have led to its redefinition as a steroid hormone and the proposal of its use in preventing and/or treating those diseases. This article is an update on the different non-bone or non-classical effects of “vitamin-hormone D”, and its potential preventive or therapeutic role in certain diseases, however, this review is not exhaustive. The different modalities of substitution or supplementation proposed in France by the Groupe de Recherche et d’Information sur les Ostéoporoses (GRIO) are also summarised.     

随州市碘缺乏病监测结果评价

目的　为查明随州市近年碘缺乏病（ Ｉ Ｄ Ｄ）防治效果及流行现状。方法　按５个不同地理方位随机抽取１０所小学,检查８～１０岁在校儿童的甲状腺,采用触诊法检查４０５人,同时 Ｂ 超法检查３６５人;测定被检儿童家用食盐含碘量４００份;测定被检儿童尿碘１８０人份;并对４０２名被检儿童进行 Ｉ Ｄ Ｄ 知识测试。结果　８～１０岁在校儿童甲状腺肿大率,触诊检查平均为３９５％ , Ｂ超检查平均为２７４％ ;学生合格碘盐食用率平均为９７０％ ;尿碘中位数平均为４４０．０μｇ／ Ｌ; Ｉ Ｄ Ｄ 知识测试及格率平均为９５５％ 。结论　４项消除 Ｉ Ｄ Ｄ 监测指标,均达到卫生部 Ｉ Ｄ Ｄ 消除标准。     

维生素D和肥胖

大量研究表明维生素D及维牛素D受体(VDR)与肥胖密切相关.血清25(OH)D及1,25(OH),D的浓度都与体重指数(BMI)呈负相关.潜在的原因可能是由于肥胖者活动少及着装习惯导致的日光照射少以及大量的维生素D储存于脂肪组织中所致.研究发现,补充维生素D有利于减轻体重.因此,肥胖者比非肥胖者更需要补充维生素D.只有增加安全、合适的日照时间,食用强化维生素D的食品或者补充高剂量的维牛素D才能保证体内充足的维生素D水平.     

维生素D和肥胖

大量研究表明维生素D及维牛素D受体（VDR）与肥胖密切相关.血清25（OH）D及1,25（OH）,D的浓度都与体重指数（BMI）呈负相关.潜在的原因可能是由于肥胖者活动少及着装习惯导致的日光照射少以及大量的维生素D储存于脂肪组织中所致.研究发现,补充维生素D有利于减轻体重.因此,肥胖者比非肥胖者更需要补充维生素D.只有增加安全、合适的日照时间,食用强化维生素D的食品或者补充高剂量的维牛素D才能保证体内充足的维生素D水平.     

南京市城区部分居民血清维生素D水平评估

目的了解南京市居民血清维生素D水平,为骨质疏松防治提供依据。方法 2011年6月至11月招募南京市城区≥40岁居民2 786名,其中40~49岁490人(17.6%),50~59岁1 084人(38.9%),60~69岁912人(32.7%),70~78岁300人(10.8%)。采集受试者清晨空腹静脉血,应用酶联免疫法测定血清25-羟维生素D[25OHD]浓度。以血清25OHD≥50 nmol/L和≥75 nmol/L分别定义为维生素D正常及良好,以血清25OHD25 nmol/L定义为维生素D缺乏,评估南京城区居民血清维生素D水平。采用超声骨密度仪(QUS),用超声振幅衰减(BUA)值及超声声速(SOS)值推算骨密度(BMD)。结果南京城区部分居民血清25OHD平均水平为(44.71±14.68)nmol/L,维生素D正常及良好者分别占31.7%和2.5%。40~49岁组血清25OHD平均为(43.48±14.23)nmol/L,50~59岁组为(45.33±14.49)nmol/L,60~69岁组为(44.41±14.66)nmol/L,70~78岁组为(45.36±15.97)nmol/L,4组间比较差异无统计学意义。血清25OHD缺乏者男性占4.3%(45例),女性占6.7%(117例),差异有统计学意义(P0.05);受试者BMD水平平均为(0.491±0.112)g/cm2,BMD和血清25OHD浓度呈正相关,差异有统计学意义(r=0.038,P=0.047)。结论南京市部分居民普遍存在维生素D缺乏,女性维生素D水平低于男性。     

成都地区291名绝经后女性骨密度与维生素D水平

目的了解成都地区部分绝经后妇女维生素D水平,观察血清25(OH)D3与骨密度、年龄、绝经年龄、体重指数的关系。方法用整群随机抽样方法抽取成都地区291名绝经后女性,平均年龄(63.9±9.7)岁,按每10岁为1个年龄组分组。记录身高、体重、绝经年龄等基本信息,使用双能X线吸收骨密度仪(DXA)测量腰椎2-4椎体(L2-4)、左髋关节股骨颈和全髋骨密度(BMD),用酶联免疫法测定血清25(OH)D3水平。分析绝经后女性骨量及血清25(OH)D3分布情况。结果超过半数的受试者(52.2%)患骨质疏松症,发病率随年龄增加而增高,80岁老年女性发病率达76.47%。血清25(OH)D3水平平均为18.37 ng/mL,维生素D缺乏发生率为68.38%。血清25(OH)D3水平与骨密度、年龄、绝经年龄无关,与BMI呈负相关(P=0.000)。结论成都地区部分绝经后妇女普遍存在维生素D缺乏,绝经后妇女应及时补充维生素D。     

Developing a multivariate prediction model of falls among older community-dwelling adults using measures of neuromuscular control and proprioceptive acuity: A pilot study

Objective

To examine whether measures of neuromuscular control and proprioceptive acuity were predictive of falls in an older community-dwelling population and to develop a multivariate prediction model.

Methods

Fifty-eight adults aged above 60 living independently in the community were recruited for a prospective falls study. On entry, they undertook a Sensory Organisation Test (SOT) and an Active Movement Extent Discrimination Assessment (AMEDA) and completed a short fall risk questionnaire. Participants were monitored for falls over the subsequent 12 months. Prior to analysis, falls were classified into three categories based on the difficulty of the activity being undertaken and the demands of the environment in which the fall occurred. Logistic regression was used to predict the probability of a fall.

Results

For falls occurring under the least challenging circumstances, the model fitted using the AMEDA score and two of the questions from the fall risk questionnaire, related to balance and confidence, achieved a specificity of 87% and sensitivity of 83%. Falls occurring in more challenging circumstances could not be predicted with any accuracy based on the variables recorded at inception.

Conclusions

This study highlights the importance of considering the heterogeneous nature of falls. Poorer proprioceptive acuity appears to play a role in falls occurring where neither the environment nor the activity is challenging, but not in falls occurring in other circumstances. Falls in the least-challenging circumstances affected 15% of participants, but this group was considerably more likely to have multiple falls, increasing their vulnerability to adverse consequences.