Compositional magnetic resonance imaging in the evaluation of the intervertebral disc: Axial vs sagittal T2 mapping

The aim of this study was to assess T₂ values of the lumbar intervertebral discs in the axial and sagittal plane views and assess their respective interobserver reliability. The lumbar intervertebral discs of 23 symptomatic patients (11 female; 12 male; mean age, 44.1 ± 10.6; range, 24-64 years) were examined at 3T. Region-of-interest (ROI) analysis was performed on axial and sagittal T₂ maps by two independent observers. Intraclass correlation coefficient (ICC) was assessed for every ROI. The interobserver agreement was excellent for the nucleus pulposus (NP) in the sagittal (0.951; 95% confidence interval [CI], 0.926-0.968) and axial (0.921; 95% CI, 0.845-0.955) planes. The posterior 20% region showed a higher ICC in the axial vs the sagittal assessment (0.845; 95% CI, 0.704-0.911 vs 0.819; 95% CI, 0.744-0.873). The same was true for the posterior 10%, with the axial ROI showing a higher ICC (0.923; 95% CI, 0.865-0.953 vs 0.628; 95% CI, 0.495-0.732). The intraobserver agreement was excellent for every ROI except the sagittal 10% region, which showed good performance (0.869; 95% CI, 0.813-0.909). The sagittal nucleus pulposus was the best-performing ROI with regard to intra- and interobserver agreement in the T₂ assessment of the lumbar intervertebral disc. However, the axial NP showed more stable agreements overall and across the value range. In addition, the annular analysis showed better inter- and intraobserver agreement in the axial plane view. Clinical significance: Based on the presented analysis, we highly recommend that further studies use axial T₂ mapping due to the higher intra- and interreader agreement.     

Karpale Begleitläsionen bei dislozierter distaler Radiusfraktur

Background

The functional outcome of surgically treated dislocated fractures of the distal radius is limited and does not correlate with radiographic results. Additional carpal lesions are assumed to be the cause. This study has evaluated which carpal lesions are associated with dislocated fractures of the distal radius.

Material and methods

A total of 104 consecutive patients with dislocated fractures of the distal radius were included in the study. The injured wrist was examined by radiography, computed tomography (CT) and magnetic resonance imaging (MRI) to determine additional carpal lesions.

Results

Radiographically 51 of the 104 fractures presented as type A according to the AO classification, 10 as type B and 39 as type C. The CT scan detected that only 5 of the 51 type A fractures were exclusively metaphyseal fractures. All type A fractures were associated with ligamental lesions in MRI.

Conclusions

The results of the study confirm the hypothesis that every dislocated fracture of the distal radius is a combined carpal trauma associated with additional osseous and/or ligamental lesions.     

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

Dietary Intake Relative to Cardiovascular Disease Risk Factors in Individuals With Chronic Spinal Cord Injury: A Pilot Study

Background:

The relationship between cardiovascular disease (CVD) risk factors and dietary intake is unknown among individuals with spinal cord injury (SCI).

Objective:

To investigate the relationship between consumption of selected food groups (dairy, whole grains, fruits, vegetables, and meat) and CVD risk factors in individuals with chronic SCI.

Methods:

A cross-sectional substudy of individuals with SCI to assess CVD risk factors and dietary intake in comparison with age-, gender-, and race-matched able-bodied individuals enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Dietary history, blood pressure, waist circumference (WC), fasting blood glucose, high-sensitivity C-reactive protein (hs-CRP), lipids, glucose, and insulin data were collected from 100 SCI participants who were 38 to 55 years old with SCI >1 year and compared to 100 matched control participants from the CARDIA study.

Results:

Statistically significant differences between SCI and CARDIA participants were identified in WC (39.2 vs 36.2 in.; P < .001) and high-density lipoprotein cholesterol (HDL-C; 39.2 vs 47.5 mg/dL; P < .001). Blood pressure, total cholesterol, triglycerides, glucose, insulin, and hs-CRP were similar between SCI and CARDIA participants. No significant relation between CVD risk factors and selected food groups was seen in the SCI participants.

Conclusion:

SCI participants had adverse WC and HDL-C compared to controls. This study did not identify a relationship between consumption of selected food groups and CVD risk factors.Key words: cardiovascular disease risk factors, dietary intake, spinal cord injuryCardiovascular disease (CVD) is a leading cause of death in individuals with chronic spinal cord injuries (SCIs).^1–5 This is partly because SCI is associated with several metabolic CVD risk factors, including dyslipidemia,^6–10 glucose intolerance,^6,11–14 and diabetes.^15–17 In addition, persons with SCI exhibit elevated markers of inflammation^18,19 and endothelial activation²⁰ that are correlated with higher CVD prevalence.^21–23 Obesity, and specifically central obesity, another CVD risk factor,^24–26 is also common in this population.^12,27–29Dietary patterns with higher amounts of whole grains and fiber have been shown to improve lipid abnormalities,³⁰ glucose intolerance, diabetes mellitus,^31–34 hypertension,³⁵ and markers of inflammation³⁶ in the general population. These dietary patterns are also associated with lower levels of adiposity.³¹ Ludwig et al reported that the strong inverse associations between dietary fiber and multiple CVD risk factors – excessive weight gain, central adiposity, elevated blood pressure, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), high low-density lipoprotein cholesterol (LDL-C), and high fibrinogen – were mediated, at least in part, by insulin levels.³⁷ Whole-grain food intake is also inversely associated with fasting insulin, insulin resistance, and the development of type 2 diabetes.^32,38,39Studies in the general population have also shown a positive association between the development of metabolic syndrome as well as heart disease and consumption of a Western diet, a diet characterized by high intake of processed and red meat and low intake of fruit, vegetables, whole grains, and dairy.^40,41 Red meat, which is high in saturated fat, has been shown to have an association with adverse levels of cholesterol and blood pressure and the development of obesity, metabolic syndrome, and diabetes.^40,42,43Numerous studies have shown that individuals with chronic SCI have poor diet quality.^44–49 A Canadian study found that only 26.7% of their sample was adherent to the recommendations about the consumption of fruit, vegetables, and grains from the “Eating Well with Canada’s Food Guide.”⁴⁴ Individuals with chronic SCI have also been found to have low fiber and high fat intakes when their diets were compared to dietary recommendations from the National Cholesterol Education Program,⁴⁶ the 2000 Dietary Guidelines for Americans,⁴⁹ and the recommended Dietary Reference Intakes and the Acceptable Macronutrient Distribution Range.^47,48However, unlike in the general population, the relationship between dietary intake and obesity and CVD risk factors is unknown in the chronic SCI population. If a dietary pattern consisting of higher intake of whole grains and dietary fiber is favorably associated with obesity and CVD risk factors in individuals with chronic SCI, then trials of increased intake of whole grains and fiber intake could be conducted to document health benefits and inform recommendations. The purpose of this pilot study is to investigate the association between selected food group intake and CVD risk factors in individuals with chronic SCI as compared to age-, gender-, and race-matched able-bodied individuals enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Data will also be used to plan future studies in the relatively understudied field of CVD and nutrition in individuals with SCI.     

巨噬细胞迁移抑制因子通过CC趋化因子配体2诱导巨噬细胞聚集

巨噬细胞迁移抑制因子最初是由于能抑制体外巨噬细胞随机迁移而被发现,现在它作为一种重要的调节因子参与一系列炎症性疾病过程.我们最近发现,巨噬细胞迁移抑制因子的缺失使一些由炎症介质诱发的白细胞-内皮细胞相互作用减弱,提示巨噬细胞迁移抑制因子在炎症反应中起作用的机制之一是促进白细胞聚集.……     

Electrophysiological changes in the canine atrium and ventricle during progressive hyperkalaemia: electrocardiographical correlates and the in vivo validation of in vitro predictions

The electrophysiological response to hyperkalaemia was reinvestigated in the whole dog for several reasons including: the paucity of comparative electrophysiological and electrocardiographical studies in which atrial and ventricular tissues were simultaneously investigated; the contrast between the clarity of findings in previous in vitro studies as compared with the rather conflicting results in earlier in vivo investigations; and the difficulty in validating the extrapolation from in vitro results and theory to the in vivo situation because of deficiences in the literature. Biphasic alterations in atrial and ventricular conduction times as well as excitability in response to progressively increasing hyperkalaemia were documented. The alterations in conduction times were reflected quite accurately by relevant electrocardiographical changes. Experiments in the whole animal were designed to test predictions based on membrane theory: the results offering strong support for the validity of extrapolating from the in vitro to the in vivo situation. The results of this study should help clarify and render interpretable many of the seemingly conflicting results in the literature.     

Piecemeal degranulation of mast cells in the inflammatory eyelid lesions of interleukin-4 transgenic mice. Evidence of mast cell histamine release in vivo by diamine oxidase-gold enzyme-affinity ultrastructural cytochemistry

We used light and electron microscopy to analyze the eyelid inflammation that develops in transgenic mice that overexpress interleukin-4 (IL-4; Tepper et al, Cell 62:457, 1990). Analysis of alkaline Giemsa-stained plastic sections examined by light microscopy (Dvorak et al, J Exp Med 132:558, 1970), as well as by routine transmission electron microscopy, indicated that the mast cells in the inflammatory eyelid lesions were undergoing piecemeal degranulation, a form of secretion in which the cells' cytoplasmic granules exhibit characteristic morphologic changes that are thought to be associated with the prolonged, vesicle-mediated release of the granules' constituents. Moreover, by using a newly reported enzyme affinity-gold method, which stains histamine based on binding to diamine oxidase-gold (Dvorak et al, J Histochem Cytochem 41:787, 1993), we show that these activated mast cells had released much of their histamine content. The eyelid lesions also exhibited increased numbers of mast cells; interstitial fibrosis, particularly around cutaneous nerves and blood vessels; activated fibroblasts; focal axonal damage; venules with endothelial cells containing numerous vesiculo-vacuolar organelles; and infiltrates of neutrophils and eosinophils. Our findings illustrate that overexpression of the IL-4 gene in vivo can result in eyelid lesions associated with piecemeal degranulation of mast cells, as well as tissue fibrosis and a variety of other pathologic changes. These results also represent the first direct morphologic evidence for histamine secretion by mast cells in vivo.     

Beta cyclodextrins bind,stabilize, and remove lipofuscin bisretinoids from retinal pigment epithelium

Accumulation of lipofuscin bisretinoids (LBs) in the retinal pigment epithelium (RPE) is the alleged cause of retinal degeneration in genetic blinding diseases (e.g., Stargardt) and a possible etiological agent for age-related macular degeneration. Currently, there are no approved treatments for these diseases; hence, agents that efficiently remove LBs from RPE would be valuable therapeutic candidates. Here, we show that beta cyclodextrins (β-CDs) bind LBs and protect them against oxidation. Computer modeling and biochemical data are consistent with the encapsulation of the retinoid arms of LBs within the hydrophobic cavity of β-CD. Importantly, β-CD treatment reduced by 73% and 48% the LB content of RPE cell cultures and of eyecups obtained from Abca4-Rdh8 double knock-out (DKO) mice, respectively. Furthermore, intravitreal administration of β-CDs reduced significantly the content of bisretinoids in the RPE of DKO animals. Thus, our results demonstrate the effectiveness of β-CDs to complex and remove LB deposits from RPE cells and provide crucial data to develop novel prophylactic approaches for retinal disorders elicited by LBs.The retinal pigment epithelium (RPE), strategically situated between the neural retina and the choroid blood vessels, is essential for photoreceptor (PR) function. It recycles vitamin A, which is required for the visual cycle and clears debris generated by the circadian shedding of PR outer segments (1, 2). Each RPE cell phagocytoses and digests the material produced by 30–50 overlying PRs, which shed 10% of their mass daily. The intense and continual phagocytic activity of RPE cells results in the progressive accumulation of indigestible products or “lipofuscin” in their lysosomal compartment (3, 4). Unlike lipofuscins found in other body tissues, which are composed mainly of protein, RPE lipofuscin consists predominantly of lipid-bisretinoids and only 2% protein (5). Lipofuscin bisretinoids (LBs) are vitamin A-derived side products of the visual cycle. Light converts 11-cis-retinal (11CR), the visual pigment chromophore, into all-trans-retinal (ATR), which is immediately flipped by the ATP-binding cassette transporter 4 (Abca4) transporter from the lumen of the outer segment discs to the cytoplasm, where it is reduced to inert all-trans-retinol by retinol dehydrogenase 8 (Rdh8), in mice (6, 7). Small fractions of 11CR and ATR are converted into N-retinylidine-N-ethanolamine (A2E) and other less abundant bisretinoids, which once accumulated in the lysosomes of RPE cells are refractory to all known lysosomal hydrolases (8, 9). The concept that LB accumulation causes retinal degeneration is supported by in vitro and in vivo data that show that excessive LBs are toxic for cultured RPE cells (10, 11), that photoreceptors overlying A2E-laden RPE are more prone to degeneration (12) and that excessive accumulation of LBs in Stargardt’s disease precedes macular degeneration (13). Mice carrying null mutations in Abca4 and Rdh8 develop blindness, basal laminar deposits, and focal accumulations of extracellular debris between the RPE and the Bruch membrane (drusen) (6).Here we report that a family of modified cyclic oligosaccharides, beta cyclodextrins (β-CDs), formed by seven d-glucose units, can encapsulate the hydrophobic arms of A2E within their nonpolar cavity, protect A2E from oxidation, and remove A2E from RPE cells. Our data demonstrate a direct correlation between the ability of β-CDs to perform these protective functions and their affinity for A2E.     

Associations of Adolescent Hopelessness and Self-Worth With Pregnancy Attempts and Pregnancy Desire

Objectives. We examined the associations of pregnancy desire (ambivalence or happiness about a pregnancy in the next year) and recent pregnancy attempts with hopelessness and self-worth among low-income adolescents.Methods. To evaluate independent associations among the study variables, we conducted gender-stratified multivariable logistic regression analyses with data derived from 2285 sexually experienced 9- to 18-year-old participants in the Mobile Youth Survey between 2006 and 2009.Results. Fifty-seven percent of youths reported a desire for pregnancy and 9% reported pregnancy attempts. In multivariable analyses, hopelessness was positively associated and self-worth was negatively associated with pregnancy attempts among both female and male youths. Hopelessness was weakly associated (P = .05) with pregnancy desire among female youths.Conclusions. The negative association of self-worth and the positive association of hopelessness with pregnancy attempts among young men as well as young women and the association of hopelessness with pregnancy desire among young women raise questions about why pregnancy is apparently valued by youths who rate their social and cognitive competence as low and who live in an environment with few options for material success.Rates of adolescent pregnancy and childbearing in the United States are among the highest in the developed world.1 Each year, approximately 750 000 women younger than 20 years become pregnant,2 and about 400 000 give birth.3 In the United States, adolescent pregnancy rates are about two thirds higher among non-White young women than among White young women, and childbearing rates are approximately one third higher2; 57% of births to adolescents in 2010 were to African American or Hispanic/Latino mothers.3 Surveillance data for 9th- to 12th-grade US students show that Blacks and Hispanics are more likely than Whites to engage in risk behaviors associated with pregnancy (e.g., vaginal intercourse at an early age, nonuse of hormonal contraceptives).4Race and ethnicity do not, in themselves, explain adolescent pregnancy risk. Kirby identified more than 100 antecedents of adolescent pregnancy, primarily related to the types of physical and social environments in which minority youths in the United States are disproportionately represented.5 He concluded that most risk factors, including poor school performance6 and residence in a socioeconomically disadvantaged neighborhood,7–9 reflected dysfunction, disadvantage, or disorganization. Offspring of adolescent parents or sisters of women who began childbearing in adolescence are at high risk for adolescent parenthood, suggesting a cultural or intergenerational component.8–10 Family quality, especially parent characteristics and relationships9,11–16; the quality of relationships with one’s school, residential community, and peers6,7,9,12,14; and substance use and mental health,9,17–22 are associated with pregnancy or pregnancy risk behaviors among both female and male adolescents.Youths who live in challenging social and physical environments typically have negative psychological and cognitive responses to their surroundings (e.g., low self-worth and hopelessness).23,24 Although the evidence is mixed,20–22,25,26 it is generally assumed that poor self-image, poor self-worth, and poor self-esteem in girls are associated with pregnancy or pregnancy risk markers, including early age at first vaginal intercourse and an inability to negotiate condom use. Hopelessness reflects negative expectations about future desired or valued outcomes and helplessness with respect to one’s ability to change the odds that negative outcomes will occur.27 Hopelessness has been identified as a risk marker for youth violence and self-harm and poor adult social trajectories.24,28–31 In industrialized countries, adolescent pregnancy (and the decision to continue a pregnancy) may be a consequence of a lack of hope and the perception of too few positive life options,32,33 although only a limited number of studies have directly examined hopelessness and pregnancy risk.Kogan et al. examined a related phenomenon, conventional future orientation, and found associations with decreased sexual risk taking at age 16 and avoidance of pregnancy at age 19 years.34 A 2013 study of Mobile Youth Survey (MYS) participants showed that having a positive feeling about the future was marginally associated with older age at first intercourse, a risk factor for adolescent pregnancy.35 Neither study examined female and male youths separately. Despite the health, social, and economic burdens associated with pregnancy involvement among boys,9,36,37 little is known about the psychological or cognitive correlates of adolescent paternity risk.Adolescent pregnancy and childbearing disproportionately occur among historically marginalized youths and present significant, and often lifelong, social and health risks to parents and their offspring.37 Many known antecedents, including poverty, neighborhood quality, and quality of the parental relationship, may be intractable. However, learned cognitive factors such as hopelessness and low self-worth may be modifiable.27Because of our overarching interest in identifying potentially intervenable correlates of pregnancy involvement among high-risk youths, we examined the hypotheses that hopelessness is positively associated and self-worth is negatively associated with 2 known risk markers of adolescent pregnancy: pregnancy attempts and pregnancy desire.15,26,38–42 Our analyses involved a cross-sectional sample of adolescent female and male participants in the MYS,43 a study of primarily African American and impoverished young people with little variation in their social risk for pregnancy. Because there may be gendered cultural meanings or consequences associated with early pregnancy and parenting (especially in communities where rates of adolescent pregnancy are disproportionately high) and because the psychological or cognitive correlates of pregnancy risk may vary according to gender,21,22 we examined female and male youths separately.