Urban legends series: Sjögren’s syndrome

Oral Diseases (2012) 19 , 46–58 Sjögren’s syndrome (SjS) is one of the most common autoimmune rheumatic diseases, clinically characterized by xerostomia and keratoconjunctivitis sicca. We investigated the following controversial topics: (i) Do we have reliable ways of assessing saliva production? (ii) How important are the quantity and quality of saliva? (iii) Are only anti‐SSA/Ro and anti‐SSB/La relevant for the diagnosis of SjS? (iv) Are the American‐European Consensus criteria (AECC) the best way to diagnose SjS? Results from literature searches suggested the following: (i) Despite the fact that numerous tests are available to assess salivation rates, direct comparisons among them are scarce with little evidence to suggest one best test. (ii) Recent developments highlight the importance of investigating the composition of saliva. However, more research is needed to standardize the methods of analysis and collection and refine the quality of the accumulating data. (iii) In addition to anti‐Ro/La autoantibodies, anti α‐fodrin IgA and anti‐MR3 autoantibodies seem to be promising diagnostic markers of SjS, but more studies are warranted to test their sensitivity and specificity. (iv) AECC are classification, not diagnostic criteria. Moreover, recent innovations have not been incorporated into these criteria. Consequently, treatment directed to patients diagnosed using the AECC might exclude a significant proportion of patients with SjS.     

Chronic Treatment With a Melanocortin-4 Receptor Agonist Causes Weight Loss,Reduces Insulin Resistance,and Improves Cardiovascular Function in Diet-Induced Obese Rhesus Macaques

The melanocortin-4 receptor (MC4R) is well recognized as an important mediator of body weight homeostasis. Activation of MC4R causes dramatic weight loss in rodent models, and mutations in human are associated with obesity. This makes MC4R a logical target for pharmacological therapy for the treatment of obesity. However, previous studies in rodents and humans have observed a broad array of side effects caused by acute treatment with MC4R agonists, including increased heart rate and blood pressure. We demonstrate that treatment with a highly-selective novel MC4R agonist (BIM-22493 or RM-493) resulted in transient decreases in food intake (35%), with persistent weight loss over 8 weeks of treatment (13.5%) in a diet-induced obese nonhuman primate model. Consistent with weight loss, these animals significantly decreased adiposity and improved glucose tolerance. Importantly, we observed no increases in blood pressure or heart rate with BIM-22493 treatment. In contrast, treatment with LY2112688, an MC4R agonist previously shown to increase blood pressure and heart rate in humans, caused increases in blood pressure and heart rate, while modestly decreasing food intake. These studies demonstrate that distinct melanocortin peptide drugs can have widely different efficacies and side effects.Maintenance of body weight and energy homeostasis requires balance between energy intake and expenditure and is achieved via the interaction between central and peripheral signals. The central melanocortin system is one of the key neural circuits involved in mediating the integration of information from both sites. Proopiomelanocortin is a prohormone that is processed into multiple bioactive peptides, including α-melanocyte–stimulating hormone (MSH), β-MSH, γ-MSH, and the endogenous opioid β-endorphin (1). α-MSH, or its analogs, are potent inhibitors of food intake and increase energy expenditure to promote weight loss in rodent and rhesus macaque models (2–5). Central melanocortins are involved in many physiological functions, including stress responses; however, their actions on the regulation of food intake and energy expenditure have been a focus.Melanocortin-4 receptor (MC4R) is the main melanocortin receptor involved in the regulation of food intake and energy expenditure, primarily through modulation of sympathetic outflow (6–8). MC4R has a broad distribution, including expression in several peripheral tissues, such as muscle, kidney, and lung (9). The importance of MC4R in the maintenance of body weight homeostasis is highlighted by genetic studies in humans and mice. MC4R^−/− mice are hyperphagic, have increased adipose and lean mass, and develop insulin resistance (10). In humans, mutations in the proopiomelanocortin gene (11) and the MC4R gene have a similar phenotype (12–14).Although the effects of MC4R agonists on energy/glucose homeostasis (15,16) make it an attractive target for a therapeutic agent, the potential side effects of increasing heart rate and blood pressure have been a major limitation (17). Indeed, recent studies reported by Greenfield et al. (18) showed that acute peripheral administration with a centrally acting MC4R selective agonist increased blood pressure and heart rate in moderately obese humans. There is an obvious concern in treating obese individuals with a high risk of hypertension and cardiovascular disease with a weight loss therapy that is exacerbating these same risks. In the current study, we use a diet-induced obesity (DIO) nonhuman primate model (NHP) to determine if long-term treatment with the MC4R-specific agonist BIM-22493 can reduce food intake and adiposity without adversely affecting cardiovascular function.     

Reduction in length of stay for patients undergoing oesophageal and gastric resections with implementation of enhanced recovery packages

Introduction

The high mortality and morbidity associated with resection for oesophagogastric malignancy has resulted in a conservative approach to the postoperative management of this patient group. In August 2009 we introduced an enhanced recovery after surgery (ERAS) pathway tailored to patients undergoing resection for oesophagogastric malignancy. We aimed to assess the impact of this change in practice on standard clinical outcomes.

Methods

Two cohorts were studied of patients undergoing resection for oesophagogastric malignancy before (August 2008 – July 2009) and after (August 2009 – July 2010) the implementation of the ERAS pathway. Data were collected on demographics, interventions, length of stay, morbidity and in-hospital mortality.

Results

There were 53 and 55 oesophagogastric resections undertaken respectively for malignant disease in each of the study periods. The median length of stay for both gastric and oesophageal resection decreased from 15 to 11 days (Mann– Whitney U, p<0.001) following implementation of the ERAS pathway. There was no significant increase in morbidity (gastric resection 23.1% vs 5.3% and oesophageal resection 25.9% vs 16.7%) or mortality (gastric resection no deaths and oesophageal resection 1.8% vs 3.6%) associated with the changes. There was a significant decrease in the number of oral contrast studies used following oesophageal resection, with a reduction from 21 (77.8%) in 2008–2009 to 6 (16.7%) in 2009–2010 (chi-squared test, p<0.0001).

Conclusions

The introduction of an enhanced recovery programme following oesophagogastric surgery resulted in a significant decrease in length of median patient stay in hospital without a significant increase in associated morbidity and mortality.     

Reply: The human sex ratio in New York City did not change after 11 September 2001

Sir, We thank Professor Lydersen for carefully considering our work(Catalano et al., 2006). He argues that we misled readers whenwe concluded that the sex ratio of 0.9995 observed in New YorkCity in January 2002 (the lowest among the 91 monthly cohortswe studied) would not be expected from history. He bases hisargument, as we understand it, on the assumption that we repeatedour test three, perhaps more, times and should not cite theP-value from only one test     

Optical fiber immunosensor for the detection of IgG antibody to Rift Valley fever virus in humans

This paper describes the development and evaluation of an optical fiber immunosensor (OFIS) for the detection of IgG antibody to Rift Valley fever virus (RVFV) in humans. The OFIS was based on a sandwich enzyme-linked immunosorbent assay (S-ELISA) format, whereby gamma-irradiated RVFV and control antigens were immobilized on the optical fiber surface coated with a mouse anti-RVFV antibody. Data sets derived from field-collected sera in Africa (n=242) were dichotomized according to the results of a virus neutralization test. Compared to standard colorimetric S-ELISA, the OFIS technique was more sensitive in detecting smaller quantity of specific IgG to RVFV in human sera. At cut-off value selected at a 95% accuracy level by the two-graph receiver operating characteristic analysis, the OFIS diagnostic sensitivity was 97.22% and diagnostic specificity 98.86%. Our results demonstrate that the OFIS technology reported here is highly accurate, simple to perform and has the potential to be used in a portable format.     

Seasonal trends in house dust mite allergen in children's beds over a 7-year period

BACKGROUND: House dust mite (HDM) allergy is closely linked to the expression of asthma and other allergic diseases. Understanding factors influencing variation in allergen may help in controlling allergic disease. The objective of this study was to investigate the effects of seasonal changes in climate, type of bed used in very early childhood and anti-mite interventions on HDM allergen concentration. METHODS: Participants were enrolled in a randomized-controlled trial of HDM avoidance. Der p 1 was measured in dust samples from children's beds on 13 occasions, from birth to age 5 years, between 1997 and 2004. Bed types were categorized as bassinette, cot or bed. The effects of study month, type of bed and intervention group on HDM allergen concentration were estimated by multiple linear regression. The relation between climatic variables and HDM allergen concentration was investigated using a polynomial distributed lag model. RESULTS: House dust mite allergen concentrations were initially low in cots and bassinettes in 1997/1998, peaked in bassinettes and beds between 1999 and 2001 and then slowly declined during the period 2002/2004. Seasonal fluctuations occurred with minima in summer and two- to threefold higher maxima during late autumn. Allergen peaks were correlated with relative humidity peaks 2 months previously. Seasonal changes in allergen were not affected by the HDM avoidance intervention. CONCLUSIONS: House dust mite allergen concentrations in Sydney beds fluctuate approximately two- to threefold on an annual cycle, partly determined by relative humidity, with peaks in late autumn and minima in summer. Fluctuations of this magnitude might be sufficient to influence asthma symptoms.     

Cultural competence revisited: nursing students with disabilities

The demographic profile of students in nursing schools is changing in relation to many different cultural backgrounds. Despite the potential for students with disabilities to enrich the nursing profession, nurse educators may be perpetuating historical attitudes, values, and practices that exclude students with disabilities from gaining admission or identifying themselves as people with disabilities. Educators in nursing schools continue to ask whether people with disabilities have a place in the nursing profession, while the more salient question is, "When will people with disabilities have a place in the nursing profession?" More important, as we create environments that welcome students with disabilities into the nursing profession, how does the quality of nursing care improve and become more appropriate for people with different cultural experiences? The purpose of this article is to present the value of recruiting students with disabilities into nursing schools in, order to enhance culturally competent nursing care.