DNA flow-cytometric analysis in colorectal cancer: A comparison of metastasizing and non-metastasizing tumours

The most common cause of death in patients with colorectal cancer is metastatic liver disease. In order to identify patients at a high risk of developing hepatic secondaries from colorectal cancers, DNA content was measured in metastasizing colorectal primaries (Group I, n= 32) as well as in their subsequently resected liver secondaries and in sections of non-metastasizing colorectal cancers (Group II, n= 25). A modified interpretation system involving both a DNA index and percentage of cycling cells (those in S and G2 + M phases) was developed. DNA content was measured in paraffin-embedded sections by flow cytometry using internal controls (human peripheral blood mononuclear cells) and non-malignant tissue controls (19 patients with diverticular disease). In Group I there were significantly more tumours with both abnormal ploidy (aneuploid or abnormal tetraploid peak) and > 15% cycling cells compared with Group II (Chi-squared; P= 0.034). The combination of abnormal ploidy and > 15% cycling cells was superior to Dukes’ classification for identifying metastasizing tumours (Logistic Regression; P= 0.047). However, it was not possible to discriminate between the two groups using either DNA ploidy or the percentage of cycling cells alone. The metastasizing colorectal cancers exhibited similar DNA ploidy characteristics and had a similar percentage of cycling cells compared with their liver metastases. These results suggest that tumour DNA ploidy plus the percentage of cycling cells may predict the development of liver metastases and thus survival in patients with colorectal cancer.     

Bilateral versus unilateral sudden sensorineural hearing loss.

OBJECTIVES: To analyze the clinical characteristics and treatment results between bilateral (bi-) and unilateral (uni-) sudden sensorineural hearing loss (SSNHL). STUDY DESIGN AND SETTING: A retrospective study. METHODS: Three hundred twenty-four patients with SSNHL were classified into two groups; simultaneous bi-SSNHL (n = 16) and uni-SSNHL (n = 308). We compared clinical characteristics, medical history, hearing level, and treatment results between the 2 groups. RESULTS: The incidence of bi-SSNHL was 4.9 percent of overall patients with SSNHL. Bi-SSNHL occurs more commonly in patients of older age, with preexisting diabetes mellitus, and lipid panel abnormalities compared with uni-SSNHL. Ten patients (62.5%) in the bi-SSNHL group showed hearing recovery in 1 or both ears compared with 56.5 percent of patients with uni-SSNHL. Only 12 (37.5%) of all 32 ears recovered in bi-SSNHL, which was significantly lower than in uni-SSNHL. CONCLUSION: Bi-SSNHL has a very low incidence and lower recovery rate than uni-SSNHL. Recognition of similarities and differences between bilateral and unilateral SSNHL can help in counseling and managing the patients.     

ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome

It was shown recently that mutations of the ATRX gene give rise to a severe, X-linked form of syndromal mental retardation associated with alpha thalassaemia (ATR-X syndrome). In this study, we have characterised the full-length cDNA and predicted structure of the ATRX protein. Comparative analysis shows that it is an entirely new member of the SNF2 subgroup of a superfamily of proteins with similar ATPase and helicase domains. ATRX probably acts as a regulator of gene expression. Definition of its genomic structure enabled us to identify four novel splicing defects by screening 52 affected individuals. Correlation between these and previously identified mutations with variations in the ATR-X phenotype provides insights into the pathophysiology of this disease and the normal role of the ATRX protein in vivo.      

Usefulness of optical coherence tomography to detect central serous chorioretinopathy in monkeys

Many systemic drugs can induce ocular toxicity and several ocular side‐effects have been identified in clinical studies. However, it is difficult to detect ocular toxicity in preclinical studies because of the lack of appropriate evaluation methods. Optical coherence tomography (OCT) is useful because it can provide real‐time images throughout a study period, whereas histopathology only provides images of sacrificed animals. Using OCT alongside histopathology, attempts were made to find effective approaches for screening of drug‐induced ocular toxicity in monkeys. Such approaches could be used in preclinical studies prior to human trials. Six male cynomolgus monkeys (Macaca fascicularis Raffles) were orally administered one of six candidate MAPK/ERK kinase (MEK) inhibitors. Central serous chorioretinopathy, a known side‐effect of such inhibitors, was identified in four monkeys by OCT. Artifacts generated during tissue processing meant that histopathology could not detect edematous changes. Thus, OCT is a useful tool to detect ocular toxicity which cannot be detected by histopathology in preclinical studies. Copyright © 2014 John Wiley & Sons, Ltd.     

Apnea‐related sleep fragmentation and poor vigilance in children with well‐controlled asthma

It has been reported that sleep problems and neurocognitive deficit in asthmatic children is prevalent. However, systematic studies on these problems in stable asthma using polysomnography have rarely been performed. We therefore investigated sleep and neurocognitive functioning in children with well‐controlled asthma. Forty‐three children with well‐controlled, stable asthma and 31 controls (age range: 6–9 years) were enrolled in the study. Subjects were questioned for daytime sleepiness using the Paediatric Daytime Sleepiness Scale. Complete overnight polysomnography and neurocognitive function tests were performed on all subjects. Children with stable asthma had lower pulmonary function in comparison to their age‐matched controls. Asthmatic children had a higher apnea–hypopnea index (P < 0.001) and apnea–hypopnea‐related arousal index (P < 0.001) as compared with non‐asthmatics. Deep sleep was decreased in asthmatics (P = 0.001). In the vigilance test, the mean number of correct answers was lower (P = 0.005) and the mean reaction time was slower (P = 0.002) in asthmatic children. A hierarchical multiple linear regression showed that deep sleep and apnea–hypopnea‐related arousal index were significant predictors of vigilance. The data suggest that the prevalence of paediatric sleep‐disordered breathing and sleep fragmentation could be very high among children with well‐controlled asthma. Moreover, vigilance, the ability to maintain attention and alertness, was worse in stable asthmatic children when compared with healthy controls. Sleep‐disordered breathing should be checked even in stable asthmatic children as they are at risk for developing neurobehavioural deterioration associated with frequent arousals during sleep. Furthermore, early treatment for asthma may be required in order to prevent airway remodelling that could cause sleep problems.     

Drugs for hyperlipidaemia may slow down the progression of hearing loss in the elderly: A drug repurposing study

Hearing loss in the elderly causes communication difficulties, decreased quality of life, isolation, loneliness and frustration. The aim of this study was to identify the modifiable variables that may affect the progression of hearing loss in the elderly. A case‐control study was conducted using two data sets. Data were extracted from the health examination survey of Ajou University Hospital (2010‐2014) and the Korea National Health and Nutrition Examination Survey (2009‐2012) data sets. Audiometry data were evaluated according to variables such as age, sex and drug use for underlying diseases. Logistic regression analysis was performed on the entire study population, and middle‐aged and elderly groups using odds ratios (ORs). Factors including older age, female gender and diabetes mellitus were significantly associated with hearing levels in all age groups (OR [95% confidence interval, 95% CI], 0.375 [0.388‐0.415], 1.202 [1.195‐1.208], and 1.427 [1.183‐1.721], respectively). However, when the results from the middle‐aged and elderly groups were compared, medication for hyperlipidaemia had a significantly positive effect on the preservation of hearing in the elderly group (OR [95% CI], 0.713 [0.567‐0.897]), but not in the middle‐aged group (OR [95% CI], 0.967 [0.791‐1.183]). People, especially those in the elderly group, exposed to medication for hyperlipidaemia are likely to have better hearing than those not exposed to such drugs. Thus, drugs prescribed for hyperlipidaemia may maintain hearing in the elderly. However, to overcome potential confounding—by unmeasured variables—that is present in this study, further studies must be performed with more elaborate research design and methodology.