Pathogen burden, inflammation, proliferation and apoptosis in human in-stent restenosis - Tissue characteristics compared to primary atherosclerosis

Pathogenic events leading to in-stent restenosis (ISR) are still incompletely understood. Among others, inflammation, immune reactions, deregulated cell death and growth have been suggested. Therefore, atherectomy probes from 21 patients with symptomatic ISR were analyzed by immunohistochemistry for pathogen burden and compared to primary target lesions from 20 stable angina patients. While cytomegalovirus, herpes simplex virus, Epstein-Barr virus and Helicobacter pylori were not found in ISR, acute and/or persistent chlamydial infection were present in 6/21 of these lesions (29%). Expression of human heat shock protein 60 was found in 8/21 of probes (38%). Indicated by distinct signals of CD68, CD40 and CRP, inflammation was present in 5/21 (24%), 3/21 (14%) and 2/21 (10%) of ISR cases. Cell density of ISR was significantly higher than that of primary lesions ( 977 +/- 315 vs. 431 +/- 148 cells/mm(2); p < 0.001). There was no replicating cell as shown by Ki67 or PCNA. TUNEL+ cells indicating apoptosis were seen in 6/21 of ISR specimens (29%). Quantitative analysis revealed lower expression levels for each intimal determinant in ISR compared to primary atheroma (all p < 0.05). In summary, human ISR at the time of clinical presentation is characterized by low frequency of pathogen burden and inflammation, but pronounced hypercellularity, low apoptosis and absence of proliferation. Copyright (C) 2004 S. Karger AG, Basel

Mortality in Hepatitis C Virus–Infected Patients With a Diagnosis of AIDS in the Era of Combination Antiretroviral Therapy

Chronic hepatitis C increased mortality by approximately 50% in patients with Centers for Disease Control and Prevention–defined AIDS, despite the competing mortality risks in these patients. About 20% of the deaths were liver-related, suggesting that greater hepatitis C virus awareness and treatment could increase survival

Optimizing OCT acquisition parameters for assessments of vitreous haze for application in uveitis

Detection and evaluation of inflammatory activity in uveitis is essential to the management of the condition, and yet continues to be largely dependent on subjective clinical measures. Optical coherence tomography (OCT) measurement of vitreous activity is an alternative to clinical vitreous haze scoring and has passed a number of early validation studies. In this study we aimed to evaluate the impact of ‘operator factors’ on the variability of the technique as part of the validation process, and to help evaluate its suitability for ‘real world’ use. Vitreous haze index was calculated as a ratio between the reflectivity of the vitreous and of the outer retina in each scan. Different scanning conditions were tested and their effect on the measurement is reported. Our results show that the ‘quantitative imaging’ technique of OCT-measured vitreous activity had good reliability in normal subjects under a range of ‘real world’ conditions, such as when the operator changes the averaging value. The technique was however vulnerable to highly inaccurate focussing or abnormal downward displacement of the image. OCT-based quantification of vitreous activity is a promising alternative to current subjective clinical estimates, with sufficient ‘tolerance’ to be used in routine clinical practice as well as clinical trials

impulsivity and the impact of contextual cues on instrumental behavior in alcohol dependence

Alcohol-related cues acquire incentive salience through Pavlovian conditioning and then can markedly affect instrumental behavior of alcohol-dependent patients to promote relapse. However, it is unclear whether similar effects occur with alcohol-unrelated cues. We tested 116 early-abstinent alcohol- dependent patients and 91 healthy controls who completed a delay discounting task to assess choice impulsivity, and a Pavlovian-to-instrumental transfer (PIT) paradigm employing both alcohol-unrelated and alcohol-related stimuli. To modify instrumental choice behavior, we tiled the background of the computer screen either with conditioned stimuli (CS) previously generated by pairing abstract pictures with pictures indicating monetary gains or losses, or with pictures displaying alcohol or water beverages. CS paired to money gains and losses affected instrumental choices differently. This PIT effect was significantly more pronounced in patients compared to controls, and the group difference was mainly driven by highly impulsive patients. The PIT effect was particularly strong in trials in which the instrumental stimulus required inhibition of instrumental response behavior and the background CS was associated to monetary gains. Under that condition, patients performed inappropriate approach behavior, contrary to their previously formed behavioral intention. Surprisingly, the effect of alcohol and water pictures as background stimuli resembled that of aversive and appetitive CS, respectively. These findings suggest that positively valenced background CS can provoke dysfunctional instrumental approach behavior in impulsive alcohol- dependent patients. Consequently, in real life they might be easily seduced by environmental cues to engage in actions thwarting their long-term goals. Such behaviors may include, but are not limited to, approaching alcohol

Rapid generation of chromosome-specific alphoid DNA probes using the polymerase chain reaction

Non-isotopic in situ hybridization of chromosome-specific alphoid DNA probes has become a potent tool in the study of numerical aberrations of specific human chromosomes at all stages of the cell cycle. In this paper, we describe approaches for the rapid generation of such probes using the polymerase chain reaction (PCR), and demonstrate their chromosome specificity by fluorescence in situ hybridization to normal human metaphase spreads and interphase nuclei. Oligonucleotide primers for conserved regions of the alpha satellite monomer were used to generate chromosome-specific DNA probes from somatic hybrid cells containing various human chromosomes, and from DNA libraries from sorted human chromosomes. Oligonucleotide primers for chromosome-specific regions of the alpha satellite monomer were used to generate specific DNA probes for the pericentromeric heterochromatin of human chromosomes 1, 6, 7, 17 and X directly from human genomic DNA

A qualitative study of independent fast food vendors near secondary schools in disadvantaged Scottish neighbourhoods

Background: Preventing and reducing childhood and adolescent obesity is a growing priority in many countries. Recent UK data suggest that children in more deprived areas have higher rates of obesity and poorer diet quality than those in less deprived areas. As adolescents spend a large proportion of time in school, interventions to improve the food environment in and around schools are being considered. Nutrient standards for school meals are mandatory in the UK, but many secondary pupils purchase foods outside schools at break or lunchtime that may not meet these standards. Methods: Qualitative interviews were conducted with fast food shop managers to explore barriers to offering healthier menu options. Recruitment targeted independently-owned shops near secondary schools (pupils aged c.12-17) in low-income areas of three Scottish cities. Ten interviews were completed, recorded, and transcribed for analysis. An inductive qualitative approach was used to analyse the data in NVivo 10. Results: Five themes emerged from the data: pride in what is sold; individual autonomy and responsibility; customer demand; profit margin; and neighbourhood context. Interviewees consistently expressed pride in the foods they sold, most of which were homemade. They felt that healthy eating and general wellbeing are the responsibility of the individual and that offering what customers want to eat, not necessarily what they should eat, was the only way to stay in business. Most vendors felt they were struggling to maintain a profit, and that many aspects of the low-income neighbourhood context would make change difficult or impossible. Conclusions: Independent food shops in low-income areas face barriers to offering healthy food choices, and interventions and policies that target the food environment around schools should take the neighbourhood context into consideration

Critical Dietetics and Sustainable Food Systems

In this chapter, we invite readers to consider a food system that is based on values where individual health, the health of the society (social system) and ecosystem health are of equal importance. With this as a lens, there is a clear need to move beyond the biosciences to consider transdisciplinary approaches as important for nutrition and Dietetic in today and tomorrow’s reality

Low Rate of CMV End-Organ Disease in HIV-Infected Patients Despite Low CD4+ Cell Counts and CMV Viremia: Results of ACTG Protocol A5030

To describe cytomegalovirus (CMV) end-organ disease (EOD) rate in AIDS patients with low CD4+ cell count despite HAART who were enrolled in a randomized, placebo-controlled trial of preemptive valganciclovir (VGCV) to prevent CMV EOD in those with CMV viremia

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders