Duration of action of antispasmodic agents: novel use of a mouse model as an in vivo pharmacological assay.

OBJECTIVE: Radial arteries are increasingly used as conduits for coronary artery bypass grafts, but perioperative graft vasospasm remains a concern. In vitro testing has demonstrated the efficacy of phenoxybenzamine and verapamil/nitroglycerin as topical antispasmodic agents, but their duration of action in vivo is unknown. Using an in vivo mouse model, we measured their duration of action in functioning vascular grafts, and compared this to their in vitro duration of action in ungrafted vascular segments. METHODS: Two millimetre mouse aortic segments (C57/BL6) were incubated with phenoxybenzamine, verapamil/nitroglycerin, or buffer (controls) for 15 min in organ chambers. Isometric tension responses to phenylephrine and prostaglandin F2alpha were measured at 0, 2, 6 and 12 h post-incubation. In parallel, 36 murine infrarenal aortic interposition grafts (2 mm) were performed. Twelve grafts were pre-treated (15 min) with phenoxybenzamine, 12 with verapamil/nitroglycerin and 12 remained untreated (controls). Isometric tension responses to the same agonists were measured in grafts harvested 2, 6, 13 and 23 h after surgery. RESULTS: Phenoxybenzamine prevented alpha-adrenergic vasoconstriction for up to 16 h in vivo (grafts), and 12h in vitro (ungrafted segments). Verapamil/nitroglycerin was effective for at least 2 h in vitro, but did not prevent vasoconstriction after 2 h in vivo. CONCLUSIONS: The mouse model appears to be a useful technique for assessing the pharmacological properties of antispasmodic agents in vivo. Phenoxybenzamine has an extended action in arterial grafts in vivo. Verapamil/nitroglycerin is short-lived in vivo but lasts longer in vitro. Measurements of antispasmodic duration of action in vitro should be interpreted with caution.     

Pulsed mode versus near-continuous mode delivery of diode laser photocoagulation for high-risk retinopathy of prematurity.

OBJECTIVE: To compare structural and functional outcomes and efficiency of diode laser photocoagulation for retinopathy of prematurity (ROP) when delivered in a pulsed mode versus a near-continuous mode. METHODS: A retrospective study was conducted of 138 patients who underwent diode laser photocoagulation for threshold ROP using either pulsed or near-continuous delivery. Laser-related complications and structural and functional outcomes were analyzed. Prospectively, time efficiency and total energy used were evaluated in nine infants with bilateral symmetric high-risk prethreshold ROP in which one eye of each infant was randomized to pulsed and the fellow eye to near-continuous delivery. RESULTS: There was no significant difference between groups with regards to prevalence of posterior disease (Zone 1 or posterior Zone 2) (p = 0.11), postoperative vitreous haze (p = 0.60), postoperative complications (p = 0.38), retinal detachment (p = 0.90), strabismus (p = 0.73), amblyopia (p = 0.69), or refractive error (p = 0.95). Mean time for treatment was 23 minutes using pulsed delivery versus 14 minutes per eye with near-continuous delivery (p < 0.001). The mean total power used per eye with pulsed mode delivery was 1.5 x 10(5) W versus 1.1 x 10(5) W with near-continuous delivery (p = 0.015). CONCLUSIONS: No differences in complications, functional outcome, or structural outcome were found between using pulsed mode and near-continuous mode diode laser delivery for high-risk ROP. Near-continuous laser delivery, in our hands, was more time-efficient and used less total power.     

Effects of simplifying choice tasks on estimates of taste heterogeneity in stated-choice surveys

Researchers usually employ orthogonal arrays or D-optimal designs with little or no attribute overlap in stated-choice surveys. The challenge is to balance statistical efficiency and respondent burden to minimize the overall error in the survey responses. This study examined whether simplifying the choice task, by using a design with more overlap, provides advantages over standard minimum-overlap methods. We administered two designs for eliciting HIV test preferences to split samples. Surveys were undertaken at four HIV testing locations in San Francisco, California. Personal characteristics had different effects on willingness to pay for the two treatments, and gains in statistical efficiency in the minimal-overlap version more than compensated for possible imprecision from increased measurement error.     

Geometric indices of bone strength are associated with physical activity and dietary calcium intake in healthy older women.

A population-based study on 1008 postmenopausal women identified that the 24% of women achieving high levels of PA and CI had 3.4-4.4% higher femoral bone strength in axial compression and 1.7-5.2% in bending than those achieving low levels, indicating that lifestyle factors influence bone strength in the proximal femur. INTRODUCTION: Extensive research has shown that increased physical activity (PA) and calcium intake (CI) decrease the rate of bone loss; however, there is little research on how these lifestyle variables affect bone geometry. This study was designed to investigate the effects of modifiable lifestyle variables, habitual PA and dietary CI, on femoral geometry in older women. MATERIALS AND METHODS: Femoral geometry, habitual PA, and dietary CI were measured in a population-based sample of 1008 women (median age+/-interquartile range, 75+/-4years) enrolled in a randomized controlled trial (RCT) of calcium supplementation. Baseline PA and CI were assessed by validated questionnaires, and 1-year DXA scans (Hologic 4500A) were analyzed using the hip structural analysis technique. Section modulus (Z), an index of bending strength, cross-sectional area (CSA), an index of axial compression strength, subperiosteal width (SPW), and centroid position, the position of the center of mass, were measured at the femoral neck (NN), intertrochanter (IT), and femoral shaft (FS) sites. These data were divided into tertiles of PA and CI, and the results were compared using analysis of covariance (ANCOVA), with corrections for age, height, weight, and treatment (calcium/placebo). RESULTS AND CONCLUSIONS: PA showed a significant dose-response effect on CSA all hip sites (p<0.03) and Z at the narrow neck and intertrochanter sites (p<0.02). For CI, there was a dose-response effect for centroid position at the intertrochanter (p=0.03). These effects were additive, such that the women (n=240) with PA in excess of 65.5 kcal/day and CI in excess of 1039 mg/day had significantly greater CSA (NN, 4.4%; IT, 4.3%; FS, 3.4%) and Z (NN, 3.9%; IT, 5.2%). These data show a favorable association between PA and aspects of bone structural geometry consistent with better bone strength. Association between CI and bone structure was only evident in 1 of 15 variables tested. However, there was evidence that there may be additive effects, whereby women with high levels of PA and CI in excess of 1039 mg/day had significantly greater CSA (NN, 0.4%; FS, 2.1%) and Z (IT, 3.0%) than women with high PA but low CI. These data show that current public health guidelines for PA and dietary CI are not inappropriate where bone structure is the health component of interest.     

中美中学生对由父母原因引起的考试焦虑认知研究

目的：比较中国和美国的中学生对由父母原因引起的考试焦虑的认知情况。方法：采用“失败结果预期（FOE）”问卷中的由父母原因引起的考试焦虑12项，测量中美两国公立学校14、15岁的1215名中学生对考试焦虑原因的认知。结果：1．相似认知：两国学生在由父母原因引起的考试焦虑方面有类似的认知，包括父母会担心自己能否进入高一级学校、会让父母烦恼等。2．跨文化的差异：表现为中国学生更多是因为父母责备、辜负了父母期望或会让父母生气而导致考试焦虑；而美国学生更多是由于父母认为他们不能面对生活中的挑战而产生焦虑。3．性别差异：表现在美国的女中学生在7个项目上、中国的男中学生在2个项目上分别比本国异性有更大程度的焦虑（P〈0．05）。结论：中美中学生对由父母原因引起的考试焦虑方面有类似的认知，但存在文化差异和性别差异。     

In vivo detection of single cells by MRI.

The use of high-relaxivity, intracellular contrast agents has enabled MRI monitoring of cell migration through and homing to various tissues, such as brain, spinal cord, heart, and muscle. Here it is shown that MRI can detect single cells in vivo, homing to tissue, following cell labeling and transplantation. Primary mouse hepatocytes were double-labeled with green fluorescent 1.63-microm iron oxide particles and red fluorescent endosomal labeling dye, and injected into the spleens of recipient mice. This is a common hepatocyte transplantation paradigm in rodents whereby hepatocytes migrate from the spleen to the liver as single cells. One month later the animals underwent in vivo MRI and punctuated, dark contrast regions were detected scattered through the livers. MRI of perfused, fixed samples and labeled hepatocyte phantoms in combination with histological evaluation confirmed the presence of dispersed single hepatocytes grafted into the livers. Appropriate controls were used to determine whether the observed contrast could have been due to dead cells or free particles, and the results confirmed that the contrast was due to disperse, single cells. Detecting single cells in vivo opens the door to a number of experiments, such as monitoring rare cellular events, assessing the kinetics of stem cell homing, and achieving early detection of metastases.     

ISCHAEMIA-REPERFUSION INJURY TO THE INTESTINE

Ischaemia-reperfusion injury (IRI) is of obvious relevance in situations where there is an interruption of blood supply to the gut, as in vascular surgery, or in the construction of free intestinal grafts. It is now appreciated that IRI also underlies the gut dysfunction that occurs in early shock, sepsis, and trauma. The events that occur during IRI are complex. However, recent advances in cellular biology have started to unravel these underlying processes. The aim of this review is to provide an outline of current knowledge on the mechanisms and consequences of IRI. Initially, IRI appears to be mediated by reactive oxygen metabolites and, at a later stage, by the priming and activation of polymorphonuclear neutrophils (PMN). Ischaemia-reperfusion injury can diminish the barrier function of the gut, and can promote an increase in the leakage of molecules (intestinal permeability) or the passage of microbes across the wall of the bowel (bacterial trans-location). Ischaemia-reperfusion injury to the gut can result in the generation of molecules that may also harm distant tissues.     

Antisocial personality disorder, HIV risk behavior and retention in methadone maintenance therapy

In a sample of 55 consecutive methadone maintenance admissions to our clinic, 42% were diagnosed with antisocial personality disorder (ASPD) using the National Institute of Mental Health Diagnostic Interview Schedule NIMH DIS. Individuals with ASPD exhibited greater risk for HIV infection as defined by more sexual contacts, needle use and equipment sharing. Data at 1 year follow-up were obtained on this group of patients. The objective was to compare the ASPD and non-ASPD groups with regards to demographics, drug abuse history, outcome and retention in treatment. There were no significant differences between the groups on any demographic or treatment outcome variables. Survival analysis indicated that there were no group differences in treatment retention. In conclusion, although there were no differences in treatment outcome between ASPD and non-ASPD groups it is possible that ASPD patients who drop out of treatment will be at higher risk for contracting and spreading HIV within the IV drug using population. These data also suggest that in this population the diagnosis of ASPD using primarily behavioral traits as measured in the NIMH-DIS-III, has little utility in predicting treatment outcome.