Production and characterization of high titer antibodies to galactocerebroside

High titer antibodies primarily of the IgG class were produced against galactocerebroside (GalC) by including keyhole limpet hemocyanin (KLH) and supplemental M. tuberculosis in the adjuvant mixture used for immunization of rabbits. Antibody titers were determined by an ELISA in which microtiter wells were coated with liposomes containing lecithin, cholesterol and GalC. The antibodies showed reactivity with GalC and psychosine, but not glucocerebroside, sulfatide, mixed gangliosides or asialo GM1. Specificity was further demonstrated by absorption of antibodies with GalC. Binding was inhibited by galactose, but only at high concentrations. Further, the antibodies did not bind to any brain proteins on immunoblots, indicating lack of reactivity with glycoproteins which might contain a terminal galactose. Antibodies to GalC are directed against different determinants than those reacting with peanut agglutinin since the lectin will not react with GalC, and the antibodies will not react with asialo GM1. The antibodies raised to GalC by this method show specific staining for oligodendroglia in culture. Peanut agglutinin binds intensely to process-bearing GalC+ oligodendroglia, but very poorly to the membrane sheets elaborated by oligodendroglia after longer times in culture. Other process-bearing GalC-, GFAP- cells were also stained with peanut agglutinin; these cells may represent glial precursors.     

Toward a Multidimensional Measure of Pregnancy Intentions: Evidence from the United States

Widely used dichotomous categorical measures of pregnancy intentions do not represent well the complexity of factors involved in women's intentions. We used a variety of exploratory statistical methods to examine measures of pregnancy intention in the 2002 National Survey of Family Growth (N = 3,032 pregnancies). Factor analyses identified two key dimensions of pregnancy intentions (desire and mistiming) and two smaller nondimensional categories (overdue and don't care). Desire included both affective and cognitive variables, as well as partner-specific factors. Similar pregnancy-intention dimensions were found for adolescent and adult women, across socioeconomic status, and among racial and ethnic groups. Both desire and mistiming were highly predictive of the decision to abort or continue the pregnancy. These analyses strongly support prior demographic thinking about the importance of both the timing of pregnancy and wanting a baby, but suggest that multidimensional rather than simple categorical measures of pregnancy intentions should be used.     

The immunopathology of regression in benign lichenoid keratosis, keratoacanthoma and halo nevus

BACKGROUNDRegression is a phenomenon present in a variety of cutaneous lesions. It is likely that similar immunologic mechanisms explain the phenomenon of spontaneous regression occurring in the various lesions.METHODSTwenty-seven specimens, nine each of halo nevus, keratoacanthoma, and benign lichenoid keratosis, including three examples each of predominantly early, mid, and late regression were examined with antibodies to HLA-II, CD1a, CD3, CD4, CD8, CD20, CD34, CD56, and CD68.RESULTSEpidermotropism of inflammatory cells, including CD1a positive, CD68 positive, CD3 positive, and CD8 positive cells, was present in benign lichenoid keratosis and keratoacanthoma, but not in halo nevus. In halo nevus, the nests of halo nevus cells tended to be infiltrated by CD1a positive, CD68 positive, CD3 positive, and CD8 positive cells. The blood vessels exhibited endothelial cell swelling with luminal narrowing and disruption within the dermis of all lesions. The CD1a positive cells were increased in number in lesional epidermis except in keratoacanthoma lesions where the density of CD1a positive cells was increased in the epithelial lip, but decreased within the epithelial portion of the keratoacanthoma proper. Conversely, the CD8 positive cells were scarce in the dermis below the epithelial lip of the keratoacanthoma, but increased in the dermis of the neoplastic epithelium. CD1a positive cells were also seen throughout the dermal portion of the lesion, particularly at the lesion base. In halo nevus, the CD1a positive cells and CD68 positive cells within the lesions were larger than those in non-lesional skin, indicating activation. The composition of the inflammatory infiltrate varied within each lesion type according to stage of regression, but T-lymphocytes predominated.CONCLUSIONCytotoxic T-cells may be the final common denominator of regression in benign lichenoid keratosis, keratoacanthoma, and halo nevus. In halo nevus, cytotoxic T-cells may play the predominant role in regression. In keratoacanthoma and benign lichenoid keratosis, cytotoxic T-cells play a pivotal role, but additional mechanisms may also be involved in the phenomenon of regression. Benign lichenoid keratoses progress through stages of regression accompanied by varying proportions of inflammatory cells, including CD3, CD4, and CD8 positive T-lymphocytes, natural killer cells, macrophages and Langerhans cells.     

The Barriers and Facilitators to Transfer of Ultrasound-Guided Central Venous Line Skills From Simulation to Practice: Exploring Perceptions of Learners and Supervisors

Phenomenon: Ultrasound-guided central venous line insertion is currently the standard of care. Randomized controlled trials and systematic reviews show that simulation is superior to apprenticeship training. The purpose of this study is to explore, from the perspectives of participants in a simulation-training program, the factors that help or hinder the transfer of skills from simulation to practice. Approach: Purposeful sampling was used to select and study the experience and perspective of novice fellows after they had completed simulation training and then performed ultrasound-guided central venous line in practice. Seven novice pediatric intensive care unit fellows and six supervising faculty in a university-affiliated academic center in a large urban city were recruited between September 2012 and January 2013. We conducted a qualitative study using semistructured interviews as our data source, employing a constructivist, grounded theory methodology. Findings: Both curricular and real-life factors influence the transfer of skills from simulation to practice and the overall performance of trainees. Clear instructions, the opportunity to practice to mastery, one-on-one observation with feedback, supervision, and further real-life experiences were perceived as factors that facilitated the transfer of skills. Concern for patient welfare, live trouble shooting, complexity of the intensive care unit environment, and the procedure itself were perceived as real-life factors that hindered the transfer of skills. Insights: As more studies confirm the superiority of simulation training versus apprenticeship training for initial student learning, the faculty should gain insight into factors that facilitate and hinder the transfer of skills from simulation to bedside settings and impact learners' performances. As simulation further augments clinical learning, efforts should be made to modify the curricular and bedside factors that facilitate transfer of skills from simulation to practice settings.     

Portable monitors in the diagnosis of obstructive sleep apnea

The use of portable monitors (PM) devices has been demonstrated in a wide variety of investigational settings with varying results. While most devices correlate very well with in-laboratory polysomnography, some still misclassify a significant numbers of patients and have lower sensitivity. In addition, the failure rate of PM devices is higher than that of in-laboratory polysomnography, requiring repeated investigations. Nonetheless, these devices may reduce the waiting time for diagnosis and could potentially decrease costs. Cost-effectiveness studies have yet to demonstrate an advantage to using PM devices, although their employed modeling techniques may not accurately reflect prevailing practices. The majority of third-party payers do not reimburse unattended studies and consider them still to be investigational. Some health maintenance organizations have begun to recognize PM-based studies in their diagnostic algorithms and will cover their cost; others may do so on a case-by-case basis. There continues to be a dearth of evidence to support widespread implementation of PM devices for use within the general population. Larger-scale validation studies in patients with lower pretest probabilities and a wide range of comorbidities are needed.     

School-based intervention acutely improves insulin sensitivity and decreases inflammatory markers and body fatness in junior high school students

CONTEXT: Risk factors for type 2 diabetes mellitus (T2DM) include obesity, family history, dyslipidemia, a proinflammatory state, impaired insulin secretory capacity, and insulin resistance. OBJECTIVE: The aim of this study was to examine the effects of a 3- to 4-month school-based intervention consisting of health, nutrition, and exercise classes plus an aerobic exercise program on diabetes risk. DESIGN: This study was a randomized before/after controlled trial. METHODS: Seventy-three eighth-grade students in a predominantly Hispanic New York City public school were divided into a control group (studied twice without receiving the intervention) and an experimental group (studied before and after the intervention). OUTCOME MEASURES: We measured body fatness (bioelectrical impedance), insulin sensitivity, beta-cell function (insulin release in response to an iv glucose load corrected for insulin sensitivity), lipid profiles, and circulating concentrations of IL-6, C-reactive protein, adiponectin, and TNF-alpha. RESULTS: Participation in the intervention was associated with significant reductions in body fatness, insulin resistance, and circulating concentrations of C-reactive protein and IL-6, irrespective of somatotype on enrollment. CONCLUSION: Short-term school-based health, nutrition, and exercise intervention is beneficial to all students and affects multiple diabetes risk factors.     

Intersections Between Childhood Abuse and Adult Intimate Partner Violence Among Ecuadorian Women

Objectives Strong linkages exist between childhood abuse and adult intimate partner violence (IPV) among women in developed countries. Few studies examine this pattern in developing nations. This study explores the effect of childhood physical and/or psychological abuse on the likelihood of IPV among a national sample of Ecuadorian women of reproductive age. Methods Secondary data analysis was conducted on a subsample of 9,077 Ecuadorian women, utilizing the 2004 Encuesta Demografía y de Salud Materna e Infantil survey. Cross-tabulations and multivariate logistic regression models were utilized to assess whether women who report childhood abuse had a higher likelihood of reporting sexual, physical or psychological IPV during their lifetimes or within the past year. Results Levels of abuse were high. More than 30% of women reported childhood psychological or physical abuse, and 21% experienced both types of abuse. Forty percent of women reported sexual, physical or psychological IPV during their lifetimes, while 15% reported any form of IPV in the past year. The co-occurrence of childhood psychological and physical abuse was highly predictive of all forms of IPV, with less consistent associations for women who reported only physical or only psychological childhood abuse. Conclusions This study suggests that childhood abuse is an important risk factor for IPV victimization among Ecuadorian women. While this analysis supports findings from developed countries, more cross-cultural research about patterns of violence throughout the life course is needed to develop relevant prevention programs.     

Stromal-mediated protection of tyrosine kinase inhibitor-treated BCR-ABL-expressing leukemia cells

Clinical studies of patients with chronic myeloid leukemia revealed that a common pattern of response is a dramatic fall in the circulating population of blast cells, with a minimal or delayed decrease in marrow blasts, suggesting a protective environment. These observations suggest that a greater understanding of the interaction of stromal cells with leukemic cells is essential. Here, we present an in vivo system for monitoring relative tumor accumulation in leukemic mice and residual disease in leukemic mice treated with a tyrosine kinase inhibitor and an in vitro system for identifying integral factors involved in stromal-mediated cytoprotection. Using the in vivo model, we observed high tumor burden/residual disease in tissues characterized as significant sources of hematopoiesis-promoting stroma, with bone marrow stroma most frequently showing the highest accumulation of leukemia in untreated and nilotinib-treated mice as well as partial protection of leukemic cells from the inhibitory effects of nilotinib. These studies, which showed a pattern of leukemia distribution consistent with what is observed in imatinib- and nilotinib-treated chronic myeloid leukemia patients, were followed by a more in-depth analysis of stroma-leukemia cell interactions that lead to protection of leukemia cells from nilotinib-induced cytotoxicity. For the latter, we used the human BCR-ABL-positive cell line, KU812F, and the human bone marrow stroma cell line, HS-5, to more closely approximate the bone marrow-associated cytoprotection observed in drug-treated leukemia patients. This in vitro system helped to elucidate stromal-secreted viability factors that may play a role in stromal-mediated cytoprotection of tyrosine kinase inhibitor-treated leukemia cells.