Altered Immune Phenotype in Peripheral Blood Cells of Patients with Scleroderma‐Associated Pulmonary Hypertension

Pulmonary arterial hypertension is a common and fatal complication of scleroderma that may involve inflammatory and autoimmune mechanisms. Alterations in the gene expression of peripheral blood mononuclear cells have been previously described in patients with pulmonary arterial hypertension. Our goal is to identify differentially expressed genes in peripheral blood mononuclear cells in scleroderma patients with and without pulmonary hypertension as biomarkers of disease.Gene expression analysis was performed on a Microarray Cohort of scleroderma patients with (n= 10) and without (n= 10) pulmonary hypertension. Differentially expressed genes were confirmed in the Microarray Cohort and validated in a Validation Cohort of scleroderma patients with (n= 15) and without (n= 19) pulmonary hypertension by RT‐qPCR. We identified inflammatory and immune‐related genes including interleukin‐7 receptor (IL‐7R) and chemokine receptor 7 as differentially expressed in patients with scleroderma‐associated pulmonary hypertension. Flow cytometry confirmed decreased expression of IL‐7R on circulating CD4+ T‐cells from scleroderma patients with pulmonary hypertension.Differences exist in the expression of inflammatory and immune‐related genes in peripheral blood cells from patients with scleroderma‐related pulmonary hypertension compared to those with normal pulmonary artery pressures. These findings may have implications as biomarkers to screen at‐risk populations for early diagnosis and provide insight into mechanisms of scleroderma‐related pulmonary hypertension. Clin Trans Sci 2010; Volume 3: 210–218     

Variation in pupil diameter in North American Gartersnakes (Thamnophis) is regulated by immersion in water, not by light intensity

A variable pupil generally regulates the amount of incoming light available for image formation on the retina. However, some of the semi-aquatic snakes (North American Gartersnakes, Thamnophis) that forage in relatively low light conditions reduce the pupil aperture in response to submergence underwater at the expense incoming light. Given that these snakes have all-cone retinas, reduction of incoming light because of pupillary constriction upon immersion seems counterintuitive. To test the effect of light and water on pupil aperture, three species of North American Gartersnakes (T. atratus, T. hammondii, and T. sirtalis) were exposed to nine light intensities in air and water. There was no effect of light on relative pupil aperture for any species. However, all three species showed a significant reduction in pupil aperture upon submergence underwater. The lack of a light response is surprising, and may be related to the method of accommodation in snakes. Snakes lack a ciliary muscle, and move the lens by constricting the pupil, which increases pressure in the posterior chamber and pushes the lens forward. Upon submergence, the snakes may be attempting to overcome the change in refractive index and defocus imposed by the water, by constricting the pupil. Thus, having the iris muscle involved in accommodation may preclude it from much of a light regulating function.     

Vaginal progesterone to prevent preterm birth in high-risk women

Preterm birth is a significant problem in the United States, contributing to neonatal morbidity and mortality. Progesterone is a hormone naturally produced by the corpus luteum and the placenta in early pregnancy and is essential for maintaining pregnancy. Clinicians and researchers have used this hormone in later gestation to try to prevent preterm birth. However, mechanisms of action, indications for use, dosing and administration have varied and are not fully understood. This article revisits two recent randomized controlled trials in which researchers investigated the effectiveness of vaginal progesterone suppositories and gel in the prevention of preterm birth among women who were at high risk for delivering prematurely.     

头颈部放疗患者涎液表皮生长因子水平降低的研究

本文主要目的是测量头颈部放疗者的涎液表皮生长因子(epidermal growth factor,EGF)水平,并评价EGF与放疗性口腔粘膜炎严重程度是否相关。 材料和方法 将13例头颈部放疗患者和18例与之性别、年龄相当的健康人进行配对研究。在放疗前、中、后分别收集全涎液,测定涎液全蛋白(totalprotein,TP)和EGF浓度,并记录口腔粘膜炎严重程度。 结果和讨论 放疗前涎液EGF和标准化EGF水平及TP水平在放疗组和健康组间的差异不明显。     

Reliability of the acetabular teardrop as a landmark

Summary This study investigated the effect of tilt and observer reliability on radiographic measurements of the position of a prosthetic acetabular cup in seven dry bone pelves using the teardrop as a landmark. Coronal or sagittal tilt of more than five degrees was easily recognisable and there was effectively no observer variation in the measurements up to this limit. In addition, 90 out of 100 randomly selected antero-posterior pelvic radiographs from an outpatient department were not significantly rotated and 93 demonstrated a clearly defined teardrop. Measurements about the teardrop on routine radiographs are therefore sufficiently accurate to allow assessment of prosthetic position.

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La valeur du sourcil cotyloidien comme repère d'analyse radiologique

Résumé Cette étude, conduite sur 7 bassins secs, apprécie l'effet de l'inclinaison du bassin sur la qualité de l'analyse radiographique de la position d'une cupule prothétique de hanche en utilisant le sourcil cotyloïdien comme repère. Une inclinaison du bassin dans les plans coronal et sagittal est aisément détectable et il n'existe pas de variation d'analyse entre les différents observateurs en dessous de 5° d'inclinaison. De plus, sur 100 radiographies antéro-postérieures de bassin choisies au hasard dans les dossiers de consultation, 90 avaient été réalisées sans incidence particulièrement adaptée et l'on pouvait repérer facilement le sourcil sur 93% d'entre elles. Les mesures faites sur des radios de routine sont donc suffisamment précises pour permettre l'évaluation de la position d'une prothèse à partir du sourcil cotyloïdien.

     

Single-arc volumetric-modulated arc therapy can provide dose distributions equivalent to fixed-beam intensity-modulated radiation therapy for prostatic irradiation with seminal vesicle and/or lymph node involvement

Objectives

Volumetric-modulated arc therapy (VMAT) is becoming an increasingly utilised modality for treating a variety of anatomical sites. However, the efficacy of single-arc VMAT to treat prostate cancer suspicious for extraprostatic extension was heretofore unknown. In this work, we report our institutional experience with single-arc VMAT and fixed-beam intensity-modulated radiation therapy (IMRT) for prostate cancer patients treated for seminal vesicle and/or lymph node involvement.

Methods

Single-arc VMAT and 7- or 9-field IMRT treatment plans were compared for 10 prostate cancer patients treated for seminal vesicle involvement and/or lymph node involvement. All treatment plans were constructed using the Philips Pinnacle treatment planning system (v.9.0, Fitchburg, WI) and delivered on an Elekta Infinity radiotherapy accelerator (Crawley, UK). Resulting plans were compared using metrics that characterised dosimetry and delivery efficiency.

Results

No statistically significant differences in target coverage, target homogeneity or normal tissue doses were noted between the plans (p>0.05). For prostate patients treated for seminal vesicle involvement, VMAT plans were delivered in 1.4±0.1 min (vs 9.5±2.4 min for fixed-beam IMRT) (p<0.01) and required approximately 20% fewer monitor units (p=0.01). For prostate patients treated for lymph node involvement, VMAT plans were delivered in 1.4±0.1 min (vs 11.7±1.3 min for fixed-beam IMRT) (p<0.01) and required approximately 45% fewer monitor units (p<0.01).

Conclusion

Single-arc VMAT plans were dosimetrically equivalent to fixed-beam IMRT plans with significantly improved delivery efficiency.The evolution and widespread implementation of intensity-modulated radiation therapy (IMRT) has enabled the delivery of highly conformal doses to target structures [1,2]. Recent advances in treatment planning optimisation and accelerator delivery technology have fuelled a growing interest in maintaining IMRT-quality treatment plans while dramatically decreasing the time and monitor unit (MU) requirements for treatment delivery, the benefits of which are well documented [3-5]. Volumetric-modulated arc therapy (VMAT), in which continuous modulation of the multileaf collimator (MLC), dose rate and gantry speed are utilised to deliver highly conformal dose distributions in a short period of time and with fewer MUs, offers such a solution [3]. However, debate has arisen regarding the efficacy and potential benefits of VMAT [5-8], particularly as it relates to the relationship between plan quality and the number of arcs required to deliver IMRT-quality plans. As such, the theoretical advantages of single-arc rotational IMRT have not yet been fully demonstrated clinically.Studies reporting the equivalence of single-arc VMAT and IMRT in the pelvis have concentrated on relatively simple, single-dose targets such as the prostate or prostate bed [4,9], while studies that have examined more complex pelvic target geometries have yielded mixed results. In a retrospective planning study, Guckenberger et al [10] found that VMAT plans including a simultaneously delivered integrate boost could improve target coverage and homogeneity for prostate cancer cases. However, their study was conducted with an early research release of treatment planning software and resulting plans were neither clinically delivered nor verified. More recently, Yoo et al [11] found that fixed-beam IMRT plans were superior to one- and two-arc VMAT when considering target volumes that included the prostate, seminal vesicles and/or pelvic lymph nodes. However, their study was conducted using the Varian Medical Systems (Palo Alto, CA) treatment planning system and delivery technology. There have been no studies to date that have conducted a similar clinical investigation using competing hardware and software configurations. Such studies are prudent given the marked differences between treatment planning and delivery approaches among radiotherapy vendors.In this work, we report on our institutional experience comparing fixed-beam IMRT and single-arc VMAT plans produced using the Philips Pinnacle treatment planning system (v.9.0, Fitchburg, WI) and delivered by the Elekta treatment control system (Crawley, UK) for 10 prostate patients treated for seminal vesicle and/or lymph node involvement. Resulting plans were compared on the basis of quantitative dosimetric metrics and delivery efficiency.