Tear film,contact lenses and tear biomarkers

This article summarises research undertaken since 1993 in the Willcox laboratory at the University of New South Wales, Sydney on the tear film, its interactions with contact lenses, and the use of tears as a source of biomarkers for ocular and non‐ocular diseases. The proteome, lipidome and glycome of tears all contribute to important aspects of the tear film, including its structure, its ability to defend the ocular surface against microbes and to help heal ocular surface injuries. The tear film interacts with contact lenses in vivo and interactions between tears and lenses can affect the biocompatibility of lenses, and may be important in mediating discomfort responses during lens wear. Suggestions are made for follow‐up research.     

Inflammatory bowel disease and the X chromosome

A review of documented cases demonstrates a significant association of Turner's syndrome with Crohn's disease and ulcerative colitis; this association relates particularly to genetic constitutions comprising an abnormal rather than an absent X chromosome. The karyotype 46XiXq, in pure or mosaic form, appears to be a significant susceptibility factor for inflammatory bowel disease. This karyotype often gives rise to relatively weak phenotypic characteristics of Turner's syndrome, which may be overlooked in short females with inflammatory bowel disease. The association of inflammatory bowel disease with Turner's syndrome may reflect the presence on the X chromosome of genes involved in disease pathogenesis. Linkage analysis studies, involving microsatellite markers on the X chromosome, are being performed.      

Reducing overdiagnosis by polygenic risk-stratified screening: findings from the Finnish section of the ERSPC

Background:

We derived estimates of overdiagnosis by polygenic risk groups and examined whether polygenic risk-stratified screening for prostate cancer reduces overdiagnosis.

Methods:

We calculated the polygenic risk score based on genotypes of 66 known prostate cancer loci for 4967 men from the Finnish section of the European Randomised Study of Screening for Prostate Cancer. We stratified the 72 072 men in the trial into those with polygenic risk below and above the median. Using a maximum likelihood method based on interval cancers, we estimated the mean sojourn time (MST) and episode sensitivity. For each polygenic risk group, we estimated the proportion of screen-detected cancers that are likely to be overdiagnosed from the difference between the observed and expected number of screen-detected cancers.

Results:

Of the prostate cancers, 74% occurred among men with polygenic risk above population median. The sensitivity was 0.55 (95% confidence interval (CI) 0.45–0.65) and MST 6.3 (95% CI 4.2–8.3) years. The overall overdiagnosis was 42% (95% CI 37–52) of the screen-detected cancers, with 58% (95% CI 54–65) in men with the lower and 37% (95% CI 31–47) in those with higher polygenic risk.

Conclusion:

Targeting screening to men at higher polygenic risk could reduce the proportion of cancers overdiagnosed.     

The Self-Overlap Method for Assessment of Lung Nodule Morphology in Chest CT

Surface morphology is an important indicator of malignant potential for solid-type lung nodules detected at CT, but is difficult to assess subjectively. Automated methods for morphology assessment have previously been described using a common measure of nodule shape, representative of the broad class of existing methods, termed area-to-perimeter-length ratio (APR). APR is static and thus highly susceptible to alterations by random noise and artifacts in image acquisition. We introduce and analyze the self-overlap (SO) method as a dynamic automated morphology detection scheme. SO measures the degree of change of nodule masks upon Gaussian blurring. We hypothesized that this new metric would afford equally high accuracy and superior precision than APR. Application of the two methods to a set of 119 patient lung nodules and a set of simulation nodules showed our approach to be slightly more accurate and on the order of ten times as precise, respectively. The dynamic quality of this new automated metric renders it less sensitive to image noise and artifacts than APR, and as such, SO is a potentially useful measure of cancer risk for solid-type lung nodules detected on CT.     

Strategies to reduce pulmonary complications after esophagectomy

Esophagectomy,the surgical removal of all or part of the esophagus,is a surgical procedure that is associated with high morbidity and mortality.Pulmonary complications are an especially important postoperative problem.Therefore,many perioperative strategies to prevent pulmonary complications after esophagectomy have been investigated and introduced in daily clinical practice.Here,we review these strategies,including improvement of patient performance and technical advances such as minimally invasive surgery that have been implemented in recent years.Furthermore,interventions such as methylprednisolone,neutrophil elastase inhibitor and epidural analgesia,which have been shown to reduce pulmonary complications,are discussed.Benefits of the commonly applied routine nasogastric decompression,delay of oral intake and prophylactic mechanical ventilation are unclear,and many of these strategies are also evaluated here.Finally,we will discuss recent insights and new developments aimed to improve pulmonary outcomes after esophagectomy.     

Inhaled corticosteroid use in HIV‐positive individuals taking protease inhibitors: a review of pharmacokinetics,case reports and clinical management

As a consequence of inhibition of the hepatic cytochrome P450 3A4 isozyme, treatment with HIV protease inhibitors can result in significant drug?drug interactions. One noteworthy interaction is between protease inhibitors and inhaled or intranasal corticosteroids. This interaction can result in adrenal insufficiency and iatrogenic Cushing's syndrome (with symptoms such as rapid weight gain, obesity, facial hirsutism and swelling), as well as hypertension, osteoporosis and decreased CD4 cell count. In this paper, we review and unite pharmacokinetic data, case reports and current research regarding this drug?drug interaction in order to suggest options for the clinical management of HIV‐positive patients requiring treatment with protease inhibitors and inhaled or intranasal corticosteroids.     

Milestones in magnetic resonance imaging and transcranial sonography of movement disorders

Twenty‐five years ago, when this journal was initiated, imaging of movement disorders was in its infancy. Since that time, magnetic resonance imaging has become a standard technique that is routinely performed in patients with movement disorders in order to exclude secondary causes and in some instances to provide specific information that aids in making the diagnosis of a neurodegenerative condition. Transcranial sonography is a more recent advance and is now widely employed to aid in the diagnosis of Parkinson's disease and possibly in detecting individuals in the premotor phases of the disease. Investigations are currently under way to evaluate the value of this technique in other movement disorders. © 2011 Movement Disorder Society