Current therapeutical strategies for allergic rhinitis

Introduction: Allergic rhinitis is a common condition with increasing prevalence and is associated with several comorbid disorders such as bronchial asthma and atopic dermatitis. If allergen avoidance is not possible, allergen-specific immunotherapy is the only causal treatment option.

Areas covered: This review focuses on current treatments and the future outlook for allergic rhinitis. Pharmacotherapy includes mast cell stabilizers, antihistamines, glucocorticosteroids (GCSs), leukotriene receptor antagonists, and nasal decongestants. Nasal GCSs are currently regarded as the most effective treatment and are considered first-line therapy together with non-sedating antihistamines. The new formulation MP29-02 combines the nasal GCS fluticasone propionate with azelastine in one single spray and has achieved greater improvements than those under monotherapy with modern GCSs or antihistamines. Furthermore, this review discusses allergen immunotherapy alone and in combination with modern monoclonal antibodies.

Expert opinion: Despite the variety of medications for allergic rhinitis, ranging from general symptomatic agents like GCSs or decongestants, to more specific ones like histamine receptor or leukotriene blockers, to causal therapy like immunotherapy, many patients still experience treatment failures or unsatisfactory results. The ultimate goal may be to endotype every downstream pathway separately in order to offer patients individualized, targeted therapy with specific antibodies against the respective pathway.     

Motion‐compensated b‐tensor encoding for in vivo cardiac diffusion‐weighted imaging

Motion is a major confound in diffusion‐weighted imaging (DWI) in the body, and it is a common cause of image artefacts. The effects are particularly severe in cardiac applications, due to the nonrigid cyclical deformation of the myocardium. Spin echo‐based DWI commonly employs gradient moment‐nulling techniques to desensitise the acquisition to velocity and acceleration, ie, nulling gradient moments up to the 2nd order (M2‐nulled). However, current M2‐nulled DWI scans are limited to encode diffusion along a single direction at a time. We propose a method for designing b‐tensors of arbitrary shapes, including planar, spherical, prolate and oblate tensors, while nulling gradient moments up to the 2nd order and beyond. The design strategy comprises initialising the diffusion encoding gradients in two encoding blocks about the refocusing pulse, followed by appropriate scaling and rotation, which further enables nulling undesired effects of concomitant gradients. Proof‐of‐concept assessment of in vivo mean diffusivity (MD) was performed using linear and spherical tensor encoding (LTE and STE, respectively) in the hearts of five healthy volunteers. The results of the M2‐nulled STE showed that (a) the sequence was robust to cardiac motion, and (b) MD was higher than that acquired using standard M2‐nulled LTE, where diffusion‐weighting was applied in three orthogonal directions, which may be attributed to the presence of restricted diffusion and microscopic diffusion anisotropy. Provided adequate signal‐to‐noise ratio, STE could significantly shorten estimation of MD compared with the conventional LTE approach. Importantly, our theoretical analysis and the proposed gradient waveform design may be useful in microstructure imaging beyond diffusion tensor imaging where the effects of motion must be suppressed.     

妊娠性肝内胆汁淤积症：一项地塞米松和熊脱氧胆酸的随机、对照试验

妊娠性肝内胆汁淤积症（ICP）的主要特征是：母体难以忍受的瘙痒症，血清胆汁酸升高（≥10μmol／L）以及胎儿死亡风险的增加。最近，确定了一个与影响胎儿损害相关的界值，即血清胆汁酸≥40μmol／L。在一项双盲、安慰剂对照试验中，作研究了熊脱氧胆酸（UDCA）和地塞米松对瘙痒症、胆汁淤积的生化指标和胎儿并发症发生率的影响。为此，选取了130例患有ICP的妇女，随机分到UDCA组（1g／d，使用3周），地塞米松组（12mg／d使用1周，第2周、第3周使用安慰剂）和安慰剂组（使用3周）进行治疗。在治疗期间和治疗3周后对瘙痒症和胆汁淤积的生化指标进行分析。在分娩时记录胎儿的并发症（自发性早产，新生儿窒息，羊水、胎盘、胎膜的胎粪染色）。意向治疗分析显示仅在UDCA组中，丙氨酸转氨酶（ALT）（P=0．01）和胆红素（P=0．002）明显减少。在血清胆汁酸≥40μmol／L的ICP妇女的亚群分析中发现（n=34）UDCA对瘙痒症（减轻75％）、胆汁酸（下降79％）、ALT（降低80％）和胆红素（降低50％）也有明显效果，但对胎儿并发症发生率无影响。地塞米松并无减轻瘙痒症或降低ALT的作用，在降低胆汁酸和胆红素方面比UDCA效果差。     

Counterfactual (‘if only’) thinking in women with chronic widespread pain

The study explored the counterfactual thinking that women with chronic and widespread pain showed in response to what they themselves considered to be particularly stressful situations. Counterfactual thinking in 125 women sick‐listed due to chronic and widespread pain was investigated in terms of structure, function and control focus. The women were asked, for each of three types of problems that they indicated in a questionnaire to affect them most strongly, to describe a typical occurrence of it and to complete a counterfactual sentence in connection with it of the type ‘If only . . .’. The majority of counterfactuals pertained to predominantly somatic problems (e.g. musculo‐skeletal problems, pain and fatigue) classified as being affective rather than preparative and self‐focused rather than external, whereas in counterfactuals relating to predominantly psychological/psychosocial problems a preparative function and an external focus were more prominent. The numbers of problems listed and the numbers of situations responded to counterfactually were positively correlated. The counterfactuals, although often related to somatic problems, generally concerned psychological or psychosocial matters such as finances and paid or unpaid work. A contextual approach to elucidating counterfactual thinking based on subjects' own experiences is seen as providing valuable insight into what bothers them most. Copyright © 2006 John Wiley & Sons, Ltd.     

Clinical indications and perspectives for intraoperative cone-beam computed tomography in oral and maxillofacial surgery.

OBJECTIVES: Intraoperative cone-beam computerized tomography (CBCT) imaging has been introduced in oral and maxillofacial surgery. Using midfacial fractures as the pioneer model, this study describes the spectrum of further promising clinical indications for intraoperative CBCT and a clinical combination with intraoperative navigation. STUDY DESIGN: One hundred seventy-nine patients admitted for surgical treatment of the facial skeleton were included in the study. Intraoperatively, 3-dimensional images were generated with the mobile CBCT scanner Arcadis Orbic 3D, obtained from Siemens Medical Solutions, in a variety of indications. RESULTS: The acquisition of the data sets was uncomplicated, and image quality was sufficient to assess the postoperative result in all cases. In the example of a facial gunshot injury, a navigation system for intraoperative localization of the metal foreign bodies was used.     

Glucose concentration in the vitreous of nondiabetic and diabetic human eyes

Glycation (nonenzymatic glucosylation) of collagen may play a role in the primary pathology of the vitreous in diabetes. The extent of glycation is determined by the glucose concentration in the tissue. In this study glucose concentration was assayed in blood and vitreous samples obtained from three patient groups undergoing vitrectomy: nondiabetic patients (ND), diabetic patients with insulin-dependent diabetes mellitus (IDDM) and diabetic patients with non-insulin-dependent diabetes mellitus (NIDDM). In the ND group the glucose concentration in the vitreous (3.5 +- 1.8 mM/1) was always lower than in the blood (9.1 +- 3.5 mM/1). In the diabetic groups the vitreous glucose concentration was, with a few exceptions, generally lower than the blood glucose concentration. The vitreous glucose concentration in these groups was generally higher (IDDM 9.4+-3.3 mM/1, NIDDM 7.2+-3.9 mM/1) than in the ND group, and in 15 specimens exceeded 11 mM/1, a level increasing the probability of collagen glycation in the vitreous of diabetic patients.This study was given financial support by the Herman Järnhardt Foundation, the Inez and Joel Carlsson Foundation and by Diabetesföreningen in Malmö     

Monitoring left ventricular dilation in mice with PET.

Molecular imaging by small-animal PET is an important noninvasive means to phenotype transgenic mouse models in vivo. When investigating pathologies of the left ventricular (LV) myocardium, the serial assessment of LV volumes is important. By this, the presence of LV dilation as a sign of developing heart failure can be detected. Whereas PET is usually used to derive biochemical and molecular information, functional parameters such as ventricular volumes are generally measured using echocardiography or MRI. In this study, a novel method to monitor LV dilation in mice with PET is presented and evaluated using cardiac MRI. METHODS: A semiautomatic 3-dimensional algorithm was used to delineate the LV myocardial wall on static PET images depicting myocardial glucose metabolism ((18)F-FDG PET) for 20 mice: 10 wild-type and 10 genetically modified littermates designed to develop a dilative cardiomyopathy phenotype (cardiomyocyte-specific knockout of survivin). The volume enclosed by the 3-dimensional midmyocardial contour was calculated as a measure for LV volume for each mouse. Data were compared with ventricular volumes measured by MRI in the same animals. RESULTS: LV volumes obtained by PET and MRI correlated well (R = 0.89) for hearts with small and large left ventricles. In accordance with the hypothesis, the LV volumes were increased significantly for transgenic mice examined at an older age compared with those examined at a younger age (MRI: 160.5 +/- 25.7 microL vs. 114.7 +/- 15.2 microL [P = 0.012]; PET: 129.3 +/- 15.3 microL vs. 73.8 +/- 15.0 microL [P < 0.001], all values shown as mean +/- SD; for MRI, mean of end-diastolic and end-systolic volumes are given), whereas they did not for their wild-type littermates (MRI: 106.2 +/- 12.3 microL vs. 94.7 +/- 14.6 microL [P = 0.214]; PET: 82.6 +/- 20.9 microL vs. 65.0 +/- 16.9 microL [P = 0.185]). CONCLUSION: Evaluation and quantitation of LV dilation in both control and cardiomyopathic mice can be reliably and serially performed using small-animal PET and (18)F-FDG, yielding useful functional information in addition to metabolic data.