EAACI Guidelines on allergen immunotherapy: IgE‐mediated food allergy

Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA‐AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE‐mediated Food Allergy, aims to provide evidence‐based recommendations for active treatment of IgE‐mediated food allergy with FA‐AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post‐discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA‐AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post‐discontinuation is also suggested, but not confirmed. Adverse events during FA‐AIT have been frequently reported, but few subjects discontinue FA‐AIT as a result of these. Taking into account the current evidence, FA‐AIT should only be performed in research centers or in clinical centers with an extensive experience in FA‐AIT. Patients and their families should be provided with information about the use of FA‐AIT for IgE‐mediated food allergy to allow them to make an informed decision about the therapy.     

自体与异体移植重建膝关节前交叉韧带的关键技术

目的:探索膝关节前交叉韧带重建术的各个关键技术环节,为提高前交叉韧带修复的临床效果提供理论和实践依据。方法:通过分析与总结与前交叉韧带重建相关的文献资料,包括其手术方式、移植物的选择、骨道定位、髁间窝成形、移植物预张与张力、移植物固定等,同时结合作者的工作经验旨在进一步提高前交叉韧带重建技术。结果:①手术方式选择:膝关节镜下生物材料移植重建前交叉韧带取得比以往优良的临床效果,已得到广泛认可。多数采用单束重建,部分学者正在尝试双束重建以改善移植物生物力学性能。②移植材料的选择:包括自体和同种异体材料,其中自体骨-髌腱-骨与腘绳肌腱最为常用。骨-髌腱-骨由于两端带有骨块,固定牢靠,允许早期重返运动场,颇受年轻运动员青睐。腘绳肌腱取材切口小,术后很少出现膝前痛,但其稳定性不如骨-髌腱-骨,且术后相对容易出现骨隧道扩大。异体移植物在体内结合、重塑速度较自体移植慢,但若经过严格的供体筛选、合理的组织取材、消毒和保存,而不减弱移植物强度,仍可取得与自体移植相当的效果。③骨道位置:正确的骨道定位非常重要,骨道位置太靠前会造成髁间窝撞击和伸直受限。研究表明,术中采用骨性标志定位法要比采用软组织标志定位法准确,术中摄片有助于骨道位置的正确定位。④髁间窝成形术:髁间窝成形的目的是为了便于更清楚的观察髁间窝后侧,同时也是为了避免髁间窝撞击综合征的发生,由于髁间窝过度成形会增加关节出血、疼痛、肿胀以及骨赘生长,所以一般不主张广泛的髁间窝成形,除非术中确有必要时才进行。⑤移植物预张与张力:移植物初始张力不够会导致膝关节持续松弛,而张力过高会限制关节活动并加速关节退变。目前对于最佳的初始张力尚无确切说法。⑥固定:现在已经研制出许多不同类型的固定材料。对于骨-髌腱-骨而言,界面挤压螺钉单切口重建前交叉韧带时,股骨侧靠近关节腔侧固定,胫骨侧远离关节腔侧固定,双切口技术时胫骨侧靠近关节腔侧固定,股骨侧远离关节腔侧固定。股骨侧固定完毕后,膝关节取何角度对胫骨侧进行固定尚存争议。膝关节稍屈曲状态下固定不容易发生松弛,但正常的膝关节在前后方向上是允许有一定松弛度的。有些学者认为在膝关节完全伸直状态下固定可以避免屈曲挛缩畸形的发生并允许前后方向有轻度松弛。而有些学者认为在膝关节稍微屈曲状态下固定会更紧。结论:要真正做到解剖、生物力学、生理功能全方位重建,前交叉韧带重建技术,仍需不断完善,分子生物学、基因工程和组织工程技术的发展以及计算机辅助机器人手术的开展会使前交叉韧带重建技术日臻完善。     

鸡胚胎素对小鼠红细胞数量及免疫器官质量的影响

目的:建立血虚和免疫抑制动物模型,观察鸡胚胎低温提取物对其红细胞造血以及免疫器官质量的影响。方法:实验于2001-04/2002-09在新乡医学院药物研究室完成。①实验材料:健康昆明种小鼠50只,雌雄各半。鸡胚胎素[中国发明专利公开(公告)号:CN1748713],符合研究者申报专利时提出的质量检验标准。②鸡胚胎素对血虚模型小鼠红细胞数值及血红蛋白含量的影响:取20只小鼠,随机排列表法分为鸡胚胎素组、模型对照组,10只/组,建立失血性血虚动物模型。失血后24h当红细胞数<3.2×1012L-1、血红蛋白含量<84g/L,且小鼠外观出现皮色苍白、食欲不振等现象时,代表造模成功。次日,鸡胚胎素组给予鸡胚胎素5g/(kg·d)灌胃,模型对照组给予生理盐水20mL/(kg·d)灌胃,连续14d。分别于失血前、失血后24h、末次给鸡胚胎素后2h尾部采血测定两组红细胞数量及血红蛋白含量的变化。③鸡胚胎素对免疫抑制模型小鼠免疫器官质量的影响:取30只小鼠,随机排列表法分为鸡胚胎素组、模型对照组、正常对照组,10只/组。鸡胚胎素组给予鸡胚胎素5g/(kg·d)灌胃,模型对照组和正常对照组均灌服等量生理盐水,连续14d。在第11天上午鸡胚胎素灌胃2h后,鸡胚胎素组、模型对照组腹腔注射环磷酰胺60mg/(kg·d),连续4d,复制免疫抑制动物模型。末次给予环磷酰胺2h后颈椎脱位法处死小鼠,计算胸腺、脾脏质量指数。结果:50只小鼠均进入结果分析。①失血前及失血后24h鸡胚胎素组与模型对照组的红细胞数值、血红蛋白含量基本相似(P>0.05)。末次给鸡胚胎素后2h与模型对照组比较,鸡胚胎素组红细胞数值、血红蛋白含量均明显升高(t=3.39,P<0.01;t=2.52,P<0.05)。②末次给环磷酰胺2h后与模型对照组比较,鸡胚胎素组、正常对照组的胸腺质量指数和脾脏质量指数均明显升高(t=6.62,P<0.01;t=2.47,P<0.05)。结论:鸡胚胎素灌胃对血虚小鼠具有较好的促红细胞造血功能,同时对环磷酰胺造成的免疫器官质量下降具有明显的增重作用。     

Donor levels of serum alanine aminotransferase activity and antibody to hepatitis B core antigen associated with recipient hepatitis C and non- B, non-C outcomes

BACKGROUND: Hepatitis virus(es) that are neither hepatitis B (HBV) nor hepatitis C (HCV) (non-B, non-C [NBNC]) may be transmitted by transfusion. The present study assessed donor values for alanine aminotransferase (ALT) and antibody to hepatitis B core antigen (anti- HBc) for their association with HCV and NBNC hepatitis outcomes among allogeneic blood recipients. STUDY DESIGN AND METHODS: Data on blood donors and recipients enrolled in the Transfusion- Transmitted Viruses Study in four United States cities from 1974 through 1980 were supplemented by anti-HBc testing of donors and anti-HCV evaluation of recipients. Two statistical approaches estimated the value of these indirect tests in detecting donors associated with HCV seroconversion and NBNC hepatitis in recipients. RESULTS: For HCV cases, donor ALT alone (at > or = 60 IU/L) had a sensitivity and a specificity of 30 and 96 percent, respectively, and anti-HBc alone (at > or = 60% inhibition) had a sensitivity and specificity of 53 and 86 percent, respectively. The two markers combined had a sensitivity and a specificity of 69 and 83 percent. For NBNC hepatitis cases, each measure had low sensitivity (20%) that was not improved by using both (28%) [corrected]. CONCLUSION: The indirect tests proved to be equal in sensitivity to the first-generation anti-HCV tests. The positive predictive power of these indirect tests in the 1980s was sufficient to affect HCV incidence in studies during that period. Improved anti-HCV assays, however, replaced the need for indirect tests. The sensitivity of indirect tests for NBNC hepatitis contributed little.     

Differences in psychotropic drug prescriptions among ethnic groups in the Netherlands

Background  

Psychotropic drug use in Europe and the USA has increased in the past 20 years. The rise in mental health-care use instigated a debate about possible differences in prevalence rates between different ethnic groups in the Netherlands, although the exact differences were unknown. The aim of this study was to determine whether these minority groups were more or less likely than the native population to receive psychotropic drugs.     

Induced sputum for the diagnosis of pulmonary tuberculosis: Is it useful in clinical practice?

BACKGROUND:

Diagnosing pulmonary tuberculosis (PTB) is challenging in patients who are unable to spontaneously expectorate. Published evidence suggests that induced sputum (IS) is the least invasive and most cost-effective method of diagnosis, and should be used before fibre-optic bronchoscopy (FOB).

METHODS:

The medical records of 337 adults treated for PTB in northern Alberta between 1997 and 2007 were reviewed to determine whether local practice patterns reflect the evidence. Microbiological data were collected from the Provincial Laboratory for Public Health. Demographic information was collected from the patients’ charts.

RESULTS:

A total of 8.5% (26 of 307) of PTB patients had IS collected, whereas 35.8% (110 of 307) underwent FOB. Among FOB patients, 56.4% (62 of 110) had no sputum sent before the procedure and 29% (18 of 62) of these patients were smear positive. Only five patients referred for FOB had IS sent previously. There were no demographic factors predictive of IS use, whereas being an inpatient at a teaching facility or having a nodule or mass on chest x-ray was predictive of FOB referral. Because so few IS samples were available, not all patients had spontaneously expectorated sputum, IS and FOB tests performed; thus, the calculated yields were not comparable with one another.

CONCLUSIONS:

Despite published evidence recommending IS collection before FOB referral in suspected PTB patients, clinicians in our health region appeared to prefer early FOB over IS by a large margin. This practice pattern is less cost effective and exposes patients and health care workers to greater risk. Further research is needed to identify the reasons for the underuse of sputum induction.     

Parkinsonism in Elderly Users of Haloperidol: Associated With Dose, Plasma Concentration, and Duration of Use

ABSTRACT: Factors that influence the variation in occurrence of antipsychotic-induced parkinsonism (AIP) in the elderly have not been well elucidated. The aim of this study was to investigate the association between parkinsonism in elderly users of haloperidol and prescribed dose, plasma concentration, and duration of use of haloperidol in a cross-sectional design. This study included 150 inpatients aged 65 years and older who were treated with haloperidol. Parkinsonism assessed by the Simpson Angus Scale was present in 46% of the included patients. Prescribed haloperidol dose varied from 0.3 to 5 mg/d. Plasma concentration ranged from 0.13 to 4.11 μg/L, with one outlying measurement (21.43 μg/L). Dose is moderate but significantly associated with haloperidol plasma concentration (weighted R = 0.32; P < 0.001). Variability in the total score on the Simpson Angus Scale could not be explained by the variability in dose, concentration (respectively R = 0.003 and 0.001) nor duration of use of haloperidol. Smoking showed to be not significantly protective in the development of AIP (crude odds ratio, 0.39; 95% confidence interval, 0.15-0.997; and adjusted odds ratio, 0.44; 95% confidence interval, 0.17-1.17). In a clinical practice-setting dose, neither plasma concentration nor duration of use of haloperidol is associated with an increased occurrence of AIP. This study does not support the hypothesis of the peripheral pharmacokinetic explanation for the high prevalence of AIP and differences in AIP sensitivity in the elderly during treatment with haloperidol.     

In vivo [123I]CNS‐1261 binding to D‐serine‐activated and MK801‐blocked NMDA receptors: A storage phosphor imaging study in rats

Disturbances of activity of the glutamatergic neurotransmitter system in the brain are present in many neuropsychiatric disorders. The N‐methyl‐D ‐aspartate (NMDA) receptor is the most abundant receptor of the glutamatergic system. In the neurodegenerative events of Alzheimer's disease, excessive activation of NMDA receptors may contribute to neuronal death. Inhibition of NMDA receptor activation may have neuroprotective effects and (semi)quantitative imaging of the activated system may help in the selection of patients for such inhibition therapies. In this study we evaluated [¹²³I]CNS‐1261 binding in the rat brain. This radiotracer binds in vivo to the MK801 binding site of activated NMDA receptors. To determine the optimal time point for ex vivo assessments after bolus injection [¹²³I]CNS‐1261 binding in rats, we performed a time course biodistribution study using dissection techniques. [¹²³I]CNS‐1261 binding was also studied in the rat brain using autoradiography by means of storage phosphor imaging, with prior facilitation of NMDA receptor activation by injection of the potent coagonist D ‐serine and after blocking of the NMDA receptor binding site by MK801 injection in D ‐serine pretreated rats. Measurements of [¹²³I]CNS‐1261 uptake matched the distribution of similar tracers for the MK801 binding site of the NMDA receptor and revealed an optimal time point of 2 h post injection for the assessment of tracer distribution in the rat brain. The blocking experiments indicated specific binding of [¹²³I]CNS‐1261 to NMDA receptors but also a considerable amount of nonspecific binding. Facilitation of NMDA receptor activation by D ‐serine did not result in an enhancement of binding of the radiotracer in the NMDA receptor‐rich rat hippocampus compared to the untreated group, as measured by autoradiography. In conclusion, our study has shown that [¹²³I]CNS‐1261 binding is influenced by NMDA receptor availability. However, high nonspecific binding limits quantification and small changes in receptor availability are unlikely to be detected. Synapse 63:557–564, 2009. © 2009 Wiley‐Liss, Inc.     

Vitamin D status predicts physical performance and its decline in older persons

CONTEXT: Vitamin D deficiency is common among older people and can cause mineralization defects, bone loss, and muscle weakness. OBJECTIVE: The aim of this study was to investigate the association of serum 25-hydroxyvitamin D (25-OHD) concentration with current physical performance and its decline over 3 yr among elderly. DESIGN: The study consisted of a cross-sectional and longitudinal design (3-yr follow-up) within the Longitudinal Aging Study Amsterdam. SETTING: An age- and sex-stratified random sample of the Dutch older population was used. OTHER PARTICIPANTS: Subjects included 1234 men and women (aged 65 yr and older) for cross-sectional analysis and 979 (79%) persons for longitudinal analysis. MAIN OUTCOME MEASURE(S): Physical performance (sum score of the walking test, chair stands, and tandem stand) and decline in physical performance were measured. RESULTS: Serum 25-OHD was associated with physical performance after adjustment for age, gender, chronic diseases, degree of urbanization, body mass index, and alcohol consumption. Compared with individuals with serum 25-OHD levels above 30 ng/ml, physical performance was poorer in participants with serum 25-OHD less than 10 ng/ml [regression coefficient (B) = -1.69; 95% confidence interval (CI) = -2.28; -1.10], and with serum 25-OHD of 10-20 ng/ml (B = -0.46; 95% CI = -0.90; -0.03). After adjustment for confounding variables, participants with 25-OHD less than 10 ng/ml and 25-OHD between 10 and 20 ng/ml had significantly higher odds ratios (OR) for 3-yr decline in physical performance (OR = 2.21; 95% CI = 1.00-4.87; and OR = 2.01; 95% CI = 1.06-3.81), compared with participants with 25-OHD of at least 30 ng/ml. The results were consistent for each individual performance test. CONCLUSIONS: Serum 25-OHD concentrations below 20 ng/ml are associated with poorer physical performance and a greater decline in physical performance in older men and women. Because almost 50% of the population had serum 25-OHD below 20 ng/ml, public health strategies should be aimed at this group.