Wegener's granulomatosis: treatment and survival characteristics in a high-prevalence southern hemisphere region

Our aim was to describe the treatment and survival characteristics of Wegener's granulomatosis (WG) in Canterbury, New Zealand. The medical records of 48 patients diagnosed between 1 July 1997 and 31 December 2008 and fulfilling validated classification criteria for WG were reviewed to characterise survivorship in the province of Canterbury, New Zealand. The age at diagnosis was 61 years (range 20 to 83 years) with an equal number of males and females. Using Kaplan-Meier product-limit analysis, the probability of survival at 1 and 10 years was 91% and 62% respectively. Of the 12 deaths in the cohort, four occurred within 12 months of diagnosis: two from pulmonary haemorrhage and two from renal failure. Beyond 12 months, two patients died of renal failure, two of myocardial infarction and one from cardiac arrhythmia, one from cerebrovascular disease and two from colorectal carcinoma. The median time to relapse was 6.75 years, and the probability of relapse within 10 years was 67%. Survivorship, treatment response rate and the rate of relapse from WG in a cohort of patients from this high-prevalence southern hemisphere region were similar to that reported for northern hemisphere cohorts with a similar prevalence.     

Myeloperoxidase and oxidative stress in rheumatoid arthritis

Objective. To determine whether MPO contributes to oxidative stress and disease activity in RA and whether it produces hypochlorous acid in SF. Methods. Plasma and where possible SF were collected from 77 RA patients while 120 healthy controls supplied plasma only. MPO and protein carbonyls were measured by ELISAs. 3-Chlorotyrosine in proteins and allantoin in plasma were measured by mass spectrometry. Results. Plasma MPO concentrations were significantly higher in patients with RA compared with healthy controls [10.8?ng/ml, inter-quartile range (IQR): 7.2-14.2; P?3.2) and those with low disease activity (LDA; DAS-28 ≤3.2) (HDA 27.9?ng/ml, 20.2-34.1 vs LDA 22.1?ng/ml, 16.9-34.9; P?>?0.05). There was a significant relationship between plasma MPO and DAS-28 (r?=?0.35; P?=?0.005). Plasma protein carbonyls and allantoin were significantly higher in patients with RA compared with the healthy controls. MPO protein was significantly higher in SF compared with plasma (median 624.0?ng/ml, IQR 258.4-2433.0 vs 30.2?ng/ml, IQR 25.1-50.9; P?相似文献   

Understanding how nurse practitioners estimate patients' risk for coronary heart disease: a judgment analysis

AIM: This paper is a report of a study to examine how nurse practitioners combine information when estimating patient risk of coronary heart disease. BACKGROUND: In the United States of America and other countries, nurse practitioners are increasingly working alongside physicians in primary healthcare settings. Given this role, nurse practitioners represent an important resource in early detection of numerous diseases. Understanding how nurse practitioners use patient characteristics (cues) to form estimates of patient risk for disease may improve general disease prevention efforts. METHOD: Social judgment theory and its lens model analysis are concerned with the correspondence between a person's judgments and the environment. This approach was applied to examine how 15 nurse practitioners weighted eight risk factors for coronary heart disease, how accurate practitioners were in assessing patient risk for coronary heart disease, and how much self-insight practitioners had into their own risk estimation processes. The data were collected in 2006. RESULTS: Nurse practitioners showed moderate to high accuracy and evinced a variety of cue-weighting strategies. Insight into their own judgment policies was modest. The lens model analysis revealed that most practitioners had lower values on knowledge of the ecology than they did on cognitive control. CONCLUSION: Educational efforts aimed at improving detection of patients at risk for diseases might do better to target increasing clinicians' understanding of cue-criteria relationships, than to stress themes of consistency in evaluating patients.     

Sexting in the public domain: competing discourses in online news article comments in the USA and the UK involving teenage sexting

The current study examined the phenomenon of teenage sexting through an analysis of 1030 comments from 15 online stories in the US and the UK. Four competing messages emerged: (1) Innocuity: Is sexting a harmless or harmful activity?; (2) Comparability: Were teenagers in the past the same or different than current teenagers?; (3) Criminality: Is teenage sexting a criminal offense or a legal activity?; and (4) Sexuality: Is teenage sexting sexual exploration or sexual exploitation? The online comments indicated an overall struggle between two different discursive constructions of sexting: A discourse of normal connection and a discourse of aberrant exposure. Implications of these findings are discussed.     

Fluorescence lifetime imaging of unstained tissues: early results in human breast cancer

Fluorescence lifetime imaging (FLIM) depends on the fluorescence decay differences between tissues to generate image contrast. In the present study FLIM has been applied to fixed (but unstained) breast cancer tissues to demonstrate the feasibility of this approach for histopathological assessment. As the FLIM method relies on natural autofluorescence, it may be possible to circumvent tissue processing altogether and so FLIM has the potential to be a powerful new method of in vivo tissue imaging via an endoscopic or per-operative approach in a variety of organs, as well as a research tool for in vivo animal models of disease. Unstained, alcohol-fixed tissue samples from 13 patients were stimulated by laser pulses at 415 nm. The temporal decay of the autofluorescence was imaged over a period of 2 ns after cessation of the pulse. The decay rate at each image pixel was calculated as the 'lifetime' factor tau. A tissue classification scheme was used to define regions in each image. The average lifetimes of different tissue regions were compared. A total of 167 tissue regions were measured. Within individual fields, stroma had a larger tau (slower decay) than epithelium (p < 0.001). Within individual patients (taking the mean tau of a given tissue type across all fields from each patient), there was a statistically significant difference between benign and malignancy-associated stroma (p < 0.05). Also, benign collagen had a longer tau than benign epithelium (p < 0.05). Multivariate analysis showed a significant difference between benign stroma, malignancy-associated stroma, blood vessels, and malignant epithelium (p < 0.05). Statistically significant differences between benign and malignancy-associated stroma were obtained even with small patient numbers, indicating that lifetime-based instruments can be developed for real-time diagnostic imaging with microscopic resolution.     

Multiple immediate-early gene expression during physiological and endocrine adaptation to repeated stress

This study had three objectives: (i) to determine whether there were individual differences in the activation and adaptation of a range of immediate-early genes to repeated restraint stress, (ii) to monitor physiological responses (endocrine, cardiovascular and core temperature) and their adaptation with repeated presentations of the stressor, and (iii) to determine whether any of these indices were altered by dehydroepiandrosterone, an anti-glucocorticoid steroid known to be reduced in humans by stress. Four groups of male rats were implanted subcutaneously with either dehydroepiandrosterone or control (paraffin) pellets. They were then subjected to either a single or 14 days of restraint (60 min/day) or transferred to the testing room (unstressed). Repeatedly stressed animals and their controls were also implanted with intra-abdominal telemetric transmitters to record heart rate and core temperature. Protein products for c-fos,fos-b, c-jun and jun-b were displayed by immunocytochemistry. Areas examined included the ventrolateral septum, hypothalamic paraventricular nucleus, amygdala, locus coeruleus and nucleus of the solitary tract. Acute restraint increased Fos immunoreactivity in all of the areas examined, with the exception of the medial amygdala. The pattern of induction for Fos-B and Jun-B was similar, while c-Jun was only increased in the septum (though constitutive levels were high in most structures compared to the other proteins examined). After 14 days of restraint, immediate-early gene immunostaining was reduced in all of the areas examined, though the extent of adaptation depended on the area and immediate-early gene. In the forebrain, Fos expression adapted in the paraventricular nucleus, amygdala and septum, whereas Fos-B and c-Jun adapted incompletely in the septum. In contrast, Jun-B behaved like Fos. In the brainstem, Fos, Fos-B and Jun-B expression adapted in the nucleus of the solitary tract (but not the locus coeruleus). Corticosterone levels were still raised above baseline, but the response was blunted compared to acute stress. There was marked stress-induced hypothermia which did not adapt during the restraint session, but this returned to baseline during restraint after about five days. In contrast, stress-induced tachycardia did not change during repeated restraint. Dehydroepiandrosterone implants had no clear-cut effects on any immunostaining following acute stress, though there was a trend towards lessened adaptation of the Fos response in the septum after steroid treatment. Dehydroepiandrosterone also did not affect the cardiovascular or endocrine responses to repeated restraint. These experiments show that adaptation of the expression of multiple immediate-early genes occurs during repeated restraint, but in a site-specific pattern in the brains of male rats.     

Genome sequencing of mucosal melanomas reveals that they are driven by distinct mechanisms from cutaneous melanoma

Mucosal melanoma displays distinct clinical and epidemiological features compared to cutaneous melanoma. Here we used whole genome and whole exome sequencing to characterize the somatic alterations and mutation spectra in the genomes of ten mucosal melanomas. We observed somatic mutation rates that are considerably lower than occur in sun‐exposed cutaneous melanoma, but comparable to the rates seen in cancers not associated with exposure to known mutagens. In particular, the mutation signatures are not indicative of ultraviolet light‐ or tobacco smoke‐induced DNA damage. Genes previously reported as mutated in other cancers were also mutated in mucosal melanoma. Notably, there were substantially more copy number and structural variations in mucosal melanoma than have been reported in cutaneous melanoma. Thus, mucosal and cutaneous melanomas are distinct diseases with discrete genetic features. Our data suggest that different mechanisms underlie the genesis of these diseases and that structural variations play a more important role in mucosal than in cutaneous melanomagenesis. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.