Pegylated liposomal doxorubicin plus highly active antiretroviral therapy versus highly active antiretroviral therapy alone in HIV patients with Kaposi's sarcoma

Twenty-eight HIV patients either naive or failing highly active antiretroviral therapy (HAART)with moderate-advanced Kaposi's sarcoma (KS)were randomly chosen to initiate a new HAART regimen plus pegylated liposomal doxorubicin(PLD) or the new HAART regimen alone. After 48 weeks, better response rates were observed in the HAART plus PLD group (76% versus 20%).In HIV-infected patients with moderate-advanced KS, HAART alone may not be enough for KS response.     

Novel insight into the detailed myocardial motion and deformation of the rodent heart using high-resolution phase contrast cardiovascular magnetic resonance

Background

Phase contrast velocimetry cardiovascular magnetic resonance (PC-CMR) is a powerful and versatile tool allowing assessment of in vivo motion of the myocardium. However, PC-CMR is sensitive to motion related artifacts causing errors that are geometrically systematic, rendering regional analysis of myocardial function challenging. The objective of this study was to establish an optimized PC-CMR method able to provide novel insight in the complex regional motion and strain of the rodent myocardium, and provide a proof-of-concept in normal and diseased rat hearts with higher temporal and spatial resolution than previously reported.

Methods

A PC-CMR protocol optimized for assessing the motion and deformation of the myocardium in rats with high spatiotemporal resolution was established, and ten animals with different degree of cardiac dysfunction underwent examination and served as proof-of-concept. Global and regional myocardial velocities and circumferential strain were calculated, and the results were compared to five control animals. Furthermore, the global strain measurements were validated against speckle-tracking echocardiography, and inter- and intrastudy variability of the protocol were evaluated.

Results

The presented method allows assessment of regional myocardial function in rats with high level of detail; temporal resolution was 3.2 ms, and analysis was done using 32 circumferential segments. In the dysfunctional hearts, global and regional function were distinctly altered, including reduced global peak values, increased regional heterogeneity and increased index of dyssynchrony. Strain derived from the PC-CMR data was in excellent agreement with echocardiography (r = 0.95, p < 0.001; limits-of-agreement −0.02 ± 3.92%strain), and intra- and interstudy variability were low for both velocity and strain (limits-of-agreement, radial motion: 0.01 ± 0.32 cm/s and −0.06 ± 0.75 cm/s; circumferential strain: -0.16 ± 0.89%strain and −0.71 ± 1.67%strain, for intra- and interstudy, respectively).

Conclusion

We demonstrate, for the first time, that PC-CMR enables high-resolution evaluation of in vivo circumferential strain in addition to myocardial motion of the rat heart. In combination with the superior geometric robustness of CMR, this ultimately provides a tool for longitudinal studies of regional function in rodents with high level of detail.     

转录因子T-bet与哮喘大鼠气道炎症及川芎嗪的干预效应

目的:转录因子T-bet在支气管哮喘的发病中起重要作用,川芎嗪治疗哮喘有效。实验拟观察川芎嗪对哮喘大鼠气道炎症的影响和转录因子T-bet的调控作用。方法:实验于2005-11/2006-06在南京医科大学完成。①实验材料及分组:72只SPF级SD大鼠随机分为正常对照组、哮喘模型组、川芎嗪小剂量组(20mg/kg)、川芎嗪中剂量组(40mg/kg)、川芎嗪大剂量组(80mg/kg)和地塞米松组,每组12只。实验用磷酸川芎嗪注射液为丽珠集团利民制药厂生产)。②实验过程及评估:以卵蛋白腹腔注射并雾化吸入制备大鼠哮喘模型,末次雾化后24h内麻醉后处死大鼠。观察6组大鼠肺组织形态学变化;测定支气管壁厚度、支气管平滑肌厚度、嗜酸粒细胞和淋巴细胞数。采用免疫组织化学半定量法测定肺组织T-bet蛋白的表达;进行转录因子T-bet蛋白表达量与气道炎症的相关性分析。实验过程中对动物处置符合动物伦理学标准。结果:①哮喘模型组嗜酸粒细胞、淋巴细胞、支气管壁厚度和支气管平滑肌厚度,明显高于正常对照组相应指标(P均<0.01);与哮喘模型组比较,川芎嗪小、中、大剂量组和地塞米松组上述4项指标均减少(P均<0.01)。②哮喘模型组、川芎嗪小、中、大剂量组和地塞米松组的T-bet表达量低于正常对照组(P均<0.01);与哮喘模型组比较,川芎嗪小、中、大剂量组T-bet表达量增加(P均<0.01);随着川芎嗪剂量增加,T-bet表达量亦相应增加,川芎嗪小、中、大剂量组之间两两比较,差异均有统计学意义(P均<0.01)。③相关分析显示哮喘模型组T-bet蛋白表达量与嗜酸性粒细胞和淋巴细胞浸润数呈负相关(r=-0.81,-0.85,P<0.01),与支气管管壁厚度和支气管平滑肌厚度呈负相关(r=-0.77,-0.79,P<0.01)。结论:支气管哮喘大鼠存在T-bet低表达;川芎嗪可抑制气道炎症,增加转录因子T-bet蛋白的表达,纠正Th1/Th2失衡,从而治疗支气管哮喘。     

Open liver resection for colorectal metastases: better short- and long-term outcomes in patients potentially suitable for laparoscopic liver resection

Background:

There is no prospective randomized data comparing laparoscopic to open hepatectomy. This study compared short- and long-term outcomes in patients undergoing hepatectomy for colorectal metastases (CRM), who were suitable for either laparoscopic or open surgery.

Methods:

Data were prospectively collected from consecutive patients undergoing hepatic resection of CRM at a single centre (1987–2007). Patients who were suitable for laparoscopic resection (Group 1) were compared with patients whose tumour characteristics would best be considered for open resection (Group 2).

Results:

Out of 1152 hepatectomies, 266 (23.1%) were deemed suitable for a laparoscopic approach. The median (IQR) number of metastases was greater in Group 2 [2(1–20) vs. 1(1–10), P < 0.001], as was the mean (SD) tumour size [5.3(3.6) cm vs. 3.3(1.2) cm, P < 0.001]. The median (IQR) operation time [210 (70) min vs. 240 (90) min, P < 0.001] and blood loss [270 (265) ml vs. 355 (320) ml, P < 0.001] were less in Group 1. There was no difference in length of stay, morbidity or mortality. Patients in Group 2 had a higher R1 resection rate (14.9%) compared with Group 1 (4.5%, P < 0.001) and lower 5-year survival (37.8% vs. 44.2%, P= 0.005).

Discussion:

Current criteria for laparoscopic hepatectomy selects patients who have more straight-forward surgery, with less risk of an involved resection margin and better long-term survival, compared with patients unsuited to a laparoscopic approach. Clearly defined criteria for laparoscopic hepatectomy are essential to allow meaningful analysis of outcomes and the results of unrandomized series of laparoscopic hepatectomies must be interpreted with caution.     

Role of tissue harmonic imaging in focal hepatic lesions: comparison with conventional sonography

Background: The purpose of the present study was to compare iissue harmonic imaging (THI) and conventional sonography in focal hepatic lesions. Methods: Fifty patients with focal hepatic lesions were enrolled for study. Conventional grayscale and THI was performed in all the patients and two sets of images of the lesions were recorded (one each for THI and conventional) and assessed for fluid–solid differentiation, detail and overall image quality. These images were compared with conventional sonographic images and graded better, same or worse as per the case. Lesions were confirmed by fine‐needle aspiration cytology (FNAC)/surgery/other modalities such as computed tomography (CT) or magnetic resonance imaging (MRI). Results: Out of 50 patients with focal hepatic lesions, 21 patients had metastatic lesions (two single; 19 multiple) five patients had hepatocellular carcinoma (HCC), five patients had hydatid cysts, nine had simple hepatic cyst whereas five patients had liver abscess, three had focal fatty infiltration; and lymphoma and hemangioma were seen in one patient each. The first observer ranked THI better than standard sonography in 40 patients (80%) for fluid–solid differentiation, in 38 (76%) for detail and in 39 (78%) for overall image quality. The second observer ranked THI better than standard sonography in 39 patients (78%) for fluid–solid differentiation, in 40 (80%) for detail and in 42 (84%) for overall image quality. Tissue harmonic imaging provided additional information in eight patients (16%) and resulted in treatment alteration in three patients (6%). Conclusion: Tissue harmonic imaging was significantly better than conventional sonography for fluid–solid differentiation, detail and total image quality in focal hepatic lesions, especially in obese patients and patients with poor acoustic window.     

Endothelial TLR4 activation impairs intestinal microcirculatory perfusion in necrotizing enterocolitis via eNOS–NO–nitrite signaling

Necrotizing enterocolitis (NEC) is a devastating disease of premature infants characterized by severe intestinal necrosis and for which breast milk represents the most effective protective strategy. Previous studies have revealed a critical role for the lipopolysaccharide receptor toll-like receptor 4 (TLR4) in NEC development through its induction of mucosal injury, yet the reasons for which intestinal ischemia in NEC occurs in the first place remain unknown. We hypothesize that TLR4 signaling within the endothelium plays an essential role in NEC development by regulating perfusion to the small intestine via the vasodilatory molecule endothelial nitric oxide synthase (eNOS). Using a unique mouse system in which we selectively deleted TLR4 from the endothelium, we now show that endothelial TLR4 activation is required for NEC development and that endothelial TLR4 activation impairs intestinal perfusion without effects on other organs and reduces eNOS expression via activation of myeloid differentiation primary response gene 88. NEC severity was significantly increased in eNOS^−/− mice and decreased upon administration of the phosphodiesterase inhibitor sildenafil, which augments eNOS function. Strikingly, compared with formula, human and mouse breast milk were enriched in sodium nitrate—a precursor for enteral generation of nitrite and nitric oxide—and repletion of formula with sodium nitrate/nitrite restored intestinal perfusion, reversed the deleterious effects of endothelial TLR4 signaling, and reduced NEC severity. These data identify that endothelial TLR4 critically regulates intestinal perfusion leading to NEC and reveal that the protective properties of breast milk involve enhanced intestinal microcirculatory integrity via augmentation of nitrate–nitrite–NO signaling.     

Effect of bed head elevation during sleep in symptomatic patients of nocturnal gastroesophageal reflux

Background and Aim: Nocturnal gastro‐esophageal reflux causes heartburn and sleep disturbances impairing quality of life. Lifestyle modifications, like bed head elevation during sleep, are thought to alleviate the symptoms of gastroesophageal reflux. We tested the hypothesis that bed head elevation might decrease recumbent acid exposure compared to sleeping in a flat bed. Methods: Patients of symptomatic nocturnal reflux and documented recumbent (supine) reflux verified by esophageal pH test entered the trial. On day 1, baseline pH was measured while the patient slept on a flat bed. Then patients slept on a bed with the head end elevated by a 20‐cm block for the next 6 consecutive days from day 2 to day 7. The pH test was repeated on day 2 and day 7. Each patient acted as his own control. Results: Twenty of 24 (83.3%) patients with mean age of 36 ± 5.5 years completed the trial. The mean (± SD) supine reflux time %, acid clearance time, number of refluxes 5 min longer and symptom score on day 1 and day 7 were 15.0 ± 8.4 and 13.7 ± 7.2; P = 0.001, 3.8 ± 2.0 and 3.0 ± 1.6; P = 0.001, 3.3 ± 2.2 and 1.0 ± 1.2; P = 0.001, and 2.3 ± 0.6 and 1.5 ± 0.6; P = 0.04, respectively. The sleep disturbances improved in 13 (65%) patients. Conclusions: Bed head elevation reduced esophageal acid exposure and acid clearance time in nocturnal (supine) refluxers and led to some relief from heartburn and sleep disturbance.     

Incidence of colorectal cancer in Kashmir valley, India

Background

There is wide variation in the incidence of colorectal cancer globally and also within the same country among different racial or ethnic groups. The present population-based study was undertaken to determine the incidence of colorectal cancer in Kashmiri population which is non-migratory and ethnically homogeneous having stable food habits.

Methods

Over a period of one year, all newly diagnosed and histological proved cases of colorectal cancer in all possible areas, where such patients are diagnosed and treated were prospectively registered.

Results

A total of 212 cases of colorectal cancers were registered; of them 113 (53.3%) originated in the colon and other 99 (46.7%) in rectum. Male to female ratio was 1.2:1. The crude incidence rate of colorectal cancer was 3.65/100,000; it was 3.78 in males, and 3.50/100,000 in females. The incidence rates for colorectal cancer in Muslims and Hindus were different. The crude incidence rate for colorectal carcinoma was highest for district Srinagar 6.19/100,000 (urban area) and lowest for district Kupwara (rural area) 1.59/100,000. The highest numbers of cases were detected in the age group 55–59 years (n?=?34). The age-specific rate for colorectal carcinoma was highest in the age group 55–59 years (17.21/100,000), followed by 65–69 years (14.86/100,000). The age standardized incidence rate was 4.52/100,000 per year. The truncated age adjusted incidence rates in age group 35–64 years was 8.31/100,000; while that for colorectal carcinoma was 8.77/100,000 in males and 7.66/100,000 in females.

Conclusion

We conclude that the incidence of colorectal cancer in Kashmir valley is similar to that reported in the rest of India.     

Using behavioural insights to increase HIV self‐sampling kit returns: a randomized controlled text message trial to improve England's HIV self‐sampling service

Objectives

The aim of the study was to determine whether behaviourally informed short message service (SMS) primer and reminder messages could increase the return rate of HIV self‐sampling kits ordered online.

Methods

The study was a 2 × 2 factorial design randomized control trial. A total of 9585 individuals who ordered a self‐sampling kit from www.freetesting.hiv different SMS combinations: 1) standard reminders sent days 3 and 7 after dispatch (control); 2) primer sent 1 day after dispatch plus standard reminders; 3) behavioural insights (BI) reminders (no primer); or 4) primer plus BI reminders. The analysis was restricted to individuals who received all messages (n = 8999). We used logistic regression to investigate independent effects of the primer and BI reminders and their interaction. We explored the impact of sociodemographic characteristics on kit return as a secondary analysis.

Results

Those who received the primer and BI reminders had a return rate 4% higher than that of those who received the standard messages. We found strong evidence of a positive effect of the BI reminders (odds ratio 1.13; 95% confidence interval 1.04–1.23; P = 0.003) but no evidence for an effect of the primer, or for an interaction between the two interventions. Odds of kit return increased with age, with those aged ≥ 65 years being almost 2.5 times more likely to return the kit than those aged 25–34 years. Men who have sex with men were 1.5–4.5 times more likely to return the kit compared with other sexual behaviour and gender identity groups. Non‐African black clients were 25% less likely to return the kit compared with other ethnicities.

Conclusions

Adding BI to reminder messages was successful in improving return rates at no additional cost.