Protocol of a Phase II Randomized, Multi-Center, Double-Blind, Placebo-Controlled Trial of S-Adenosyl Methionine in Participants with Mild Cognitive Impairment or Dementia Due to Alzheimer's Disease.

BACKGROUND: S-adenosyl methionine (SAMe) is a pivotal metabolite in multiple pathways required for neuronal homeostasis, several of which are compromised in Alzheimer's disease (AD). Correction of the SAMe deficiency that is characteristic of the AD brain may attenuate or prevent pathological processes driving AD-associated neurodegeneration including aberrant tau hyperphosphorylation and DNA hypomethylation. OBJECTIVES: The primary aim is to test the hypothesis that daily treatment with 400 mg oral SAMe for 180 days will lead to a greater reduction from baseline in plasma levels of p-tau181 compared to placebo in patients with mild cognitive impairment or dementia due to AD. DESIGN, SETTING, PARTICIPANTS: This is a phase II, randomized, multi-center, double-blind, placebo-controlled trial among 60 participants with mild cognitive impairment or dementia due to AD. Participants will be randomized in a 1:1 ratio to receive either SAMe or matching placebo, to be taken as an adjunct to their AD standard of care. MEASUREMENTS AND RESULTS: The primary outcome is change in plasma p-tau181 concentration between baseline and following 180 days of treatment, which will be compared between the active and placebo group. Secondary outcomes are the safety of SAMe administration (incidence of serious adverse events), change from baseline in cognitive performance (as measured by the Repeatable Battery for the Assessment of Neuropsychological Status), and epigenetic changes in DNA methylation. CONCLUSION: Demonstration of effective and safe lowering of plasma p-tau181 with SAMe in this phase II trial would pave the way for an exciting field of translational research and a larger phase III trial.

Bactericidal and cytotoxic activity of a diarylheptanoid (etlingerin) isolated from a ginger (Etlingera pubescens) endemic to Borneo.

AIMS: The aim of this study was to investigate the antimicrobial activities of Etlingera pubescens, and to isolate and identify the antimicrobial compound. METHODS AND RESULTS: The crude extracts of E. pubescens were obtained through methanol extraction, and evaluated for antimicrobial activities. From this extract, 1,7-bis(3,4-dihydroxyphenyl)heptan-3-yl acetate (etlingerin) was isolated. When compared to curcumin (a compound with a similar chemical structure), etlingerin showed twofold lower minimum inhibitory concentration values while also being bactericidal. Through time kill assay, etlingerin showed rapid killing effects (as fast as 60 min) against the Gram-positive bacteria (Staphylococcus aureus ATCC 43300 and Bacillus subtilis ATCC 8188). Further assessment revealed that etlingerin caused leakage of intracellular materials, therefore suggesting alteration in membrane permeability as its antimicrobial mechanism. Cytotoxicity study demonstrated that etlingerin exhibited approximately 5- to 12-fold higher IC50 values against several cell lines, as compared to curcumin. CONCLUSIONS: Etlingerin isolated from E. pubescens showed better antibacterial and cytotoxic activities when compared to curcumin. Etlingerin could be safe for human use, though further cytotoxicity study using animal models is needed. SIGNIFICANCE AND IMPACT OF THE STUDY: Etlingerin has a potential to be used in treating bacterial infections due to its good antimicrobial activity, while having potentially low cytotoxicity.

False-negative MRI breast screening in high-risk women.

AIM: To determine the frequency of and reasons for false-negative breast magnetic resonance imaging (MRI) examinations in high-risk women undergoing annual screening. MATERIALS AND METHODS: The family history clinic database was interrogated and women at high risk of breast cancer who had undergone screening MRI and been diagnosed with breast cancer within 2 years of the MRI examination were identified. All available MRI examinations were reviewed and classified by two radiologists. RESULTS: Of 32 women diagnosed with breast cancer, 23 had MRI images available for review. Fourteen were diagnosed at MRI, four at interim mammography, two symptomatically, one incidentally on ultrasound, and two at risk-reducing mastectomy. Ten women (43%) had potentially avoidable delays in diagnosis. The preceding MRIs were classified as false-negative screens in five women (one prevalent, four incident), false-negative assessment in seven and minimal signs in three (three women were assigned dual classifications). Common reasons for diagnostic delay included small enhancing masses that were overlooked, areas of non-mass enhancement that showed little or no change between screens, false reassurance from normal conventional imaging at assessment, and overreliance on short-interval repeat MRI. CONCLUSION: Small enhancing foci, masses, and areas of segmental non-mass enhancement are common MRI features of early breast cancer. Lack of change of non-mass enhancement on serial examinations does not exclude malignancy. Double reading of both screening and assessment examinations is recommended. Ready access to MRI biopsy is essential. Short-interval repeat MRI should be limited to reassessing low suspicion areas likely to be benign glandular enhancement. Annual mammography remains important in these women.

A randomised pilot study comparing 13 G vacuum-assisted biopsy and conventional 14 G core needle biopsy of axillary lymph nodes in women with breast cancer.

AIM: To compare the acceptability, safety, and feasibility of vacuum-assisted biopsy (VAB) and core needle biopsy (CNB) of axillary lymph nodes in women with breast cancer. MATERIALS AND METHODS: This parallel, non-blinded, randomised study was approved by the National Research Ethics Service. Following written informed consent, women with abnormal appearing axillary lymph nodes and radiologically malignant breast masses were randomised 1:1 to lymph node sampling under local anaesthetic with either 14 G CNB or 13 G VAB in a single UK centre. Primary outcomes were study uptake rate and patient willingness to undergo a repeat procedure if necessary. Procedure duration, immediate and post-procedure pain scores, diagnostic yield, complications, and surgical histopathology were recorded. RESULTS: Ninety-five women were approached; 81 (85.3%) consented and were randomised. Forty underwent CNB; 40 underwent VAB; one was excluded. Median age was 57 years. The median procedure time was 2 minutes for both techniques. The median number of samples obtained was three for CNB and four for VAB. Median pain scores for the procedure and first 3 days were 1/10 and 1/10 for CNB and 1/10 and 2/10 for VAB (p=0.11 and 0.04). More women were prepared to undergo repeat CNB compared to VAB, but the difference was not significant (38/39 versus 33/39; p=0.11). Two patients developed a haematoma after VAB. One CNB and six VABs failed to yield adequate tissue (p=0.11), but the sensitivity was similar at 79% and 78%. CONCLUSION: Study uptake was high. Acceptability of the two procedures was similar, but VAB was associated with more post-procedure pain. The sensitivity appears to be similar.

Time trends in upper gastrointestinal diseases and Helicobacter pylori infection in a multiracial Asian population--a 20-year experience over three time periods.

BACKGROUND: Marked epidemiological changes in upper gastrointestinal diseases and Helicobacter pylori infection have taken place in the Asian Pacific region. In particular, differences with respect to race in the multiracial Asian population in Malaysia have been important and interesting. AIM: A time trend study of upper gastrointestinal disease and H. pylori infection in three time periods: 1989-1990, 1999-2000 and 2009-2010 spanning a period of 20 years was carried out. METHODS: Consecutive first time gastroscopies carried out on patients attending the University of Malaya Medical Center were studied. Diagnoses and H. pylori infection status were carefully recorded. RESULTS: A steady decline in prevalence of duodenal ulcer (DU) and gastric ulcer (GU) from 21.1% to 9.5% to 5.0% and from 11.9% to 9.4% to 9.9% while an increase in erosive oesophagitis (EO) from 2.0% to 8.4% to 9.5% (chi-square for trend; P < 0.001) for the periods 1989-1990, 1999-200 and 2009-2010 were observed. The overall prevalence of H. pylori had also decreased from 51.7% to 30.3% to 11.1% for the same periods of time. The proportion of H. pylori positive ulcers had also decreased: DU (90.1%-69.8%-28.9%) and GU (86.6-56.8%-18.9%) (P < 0.001). This was observed in Malays, Chinese and Indians but the difference over time was most marked in Malays. There was a steady decline in the proportion of patients with gastric and oesophageal cancers. CONCLUSIONS: Peptic ulcers have declined significantly over a 20-year period together with a decline in H. pylori infection. In contrast, a steady increase in erosive oesophagitis was observed. Gastric and oesophageal squamous cell cancers have declined to low levels.

Dietary patterns and cognitive decline in an Australian study of ageing.

The aim of this paper was to investigate the association of three well-recognised dietary patterns with cognitive change over a 3-year period. Five hundred and twenty-seven healthy participants from the Australian Imaging, Biomarkers and Lifestyle study of ageing completed the Cancer Council of Victoria food frequency questionnaire at baseline and underwent a comprehensive neuropsychological assessment at baseline, 18 and 36 months follow-up. Individual neuropsychological test scores were used to construct composite scores for six cognitive domains and a global cognitive score. Based on self-reported consumption, scores for three dietary patterns, (1) Australian-style Mediterranean diet (AusMeDi), (2) western diet and (3) prudent diet were generated for each individual. Linear mixed model analyses were conducted to examine the relationship between diet scores and cognitive change in each cognitive domain and for the global score. Higher baseline adherence to the AusMeDi was associated with better performance in the executive function cognitive domain after 36 months in apolipoprotein E (APOE) ɛ4 allele carriers (P<0.01). Higher baseline western diet adherence was associated with greater cognitive decline after 36 months in the visuospatial cognitive domain in APOE ɛ4 allele non-carriers (P<0.01). All other results were not significant. Our findings in this well-characterised Australian cohort indicate that adherence to a healthy diet is important to reduce risk for cognitive decline, with the converse being true for the western diet. Executive function and visuospatial functioning appear to be particularly susceptible to the influence of diet.

Imaging features, follow-up, and management of incidentally detected renal lesions.

Incidental renal masses are common findings on cross-sectional imaging. Most will be readily identified as simple cysts, but with an inexorable rise in abdominal imaging, [particularly computed tomography (CT)], coupled with a rise in the incidence of renal cancer, the likelihood of detecting a malignant mass is increasing. This review informs the radiologist which lesions can be safely ignored, which will require further imaging for accurate categorization, and which require referral for consideration of treatment. For the small proportion of lesions that are indeterminate, careful attention to imaging technique, and the use of unenhanced and contrast-enhanced CT or magnetic resonance imaging (MRI) in all but a few specific instances will accurately characterize such lesions. The figures have been chosen to illustrate specific imaging features of common renal lesions. Management options for malignant, or presumed malignant, renal masses include active surveillance, percutaneous ablation, laparoscopic or open, partial or total nephrectomy. Biopsy has a role in determining the nature of masses that remain indeterminate on cross-sectional imaging, prior to definitive treatment. Common pitfalls in assessing incidental renal lesions are emphasized; some of these are due to sub-optimal imaging techniques and others to errors in interpretation.

HPB Online: an electronic health education portal in Singapore.

In 2001, the Health Promotion Board (HPB) developed HPB Online, an internet-based health education portal to disseminate health messages. The objective of this article is to describe the structure of HPB Online, review its reach as a tool to deliver health information in Singapore, and discuss the advantages of using the internet to complement traditional media such as the television, newspapers and radio. Since its inception in 2001, the numbers of page-views, monthly visits and repeat visitors have increased markedly. The most popular webpages have consistently been Food Info Search. The average length of visit also showed a gradual increase during the study period, from about 11.0 minutes in January 2002 to 18.5 minutes in December 2004. The key advantage of using the HPB Online is that it allows quick delivery of information to the public and this is ideal for time-sensitive issues. It helps Singaporeans to make better informed decisions to maintain and to improve their health. With its high utilisation, the HPB will continue to use the internet as part of its multichannel marketing strategy to disseminate health information.

Diagnostic and interventional radiology workload in acute pancreatitis in an ITU/HDU setting.

AIM: To determine the impact on diagnostic and interventional radiology services when imaging patients with severe pancreatitis on intensive therapy (ITU) and high-dependency units (HDU) in a tertiary referral centre. MATERIAL AND METHODS: One hundred and sixty-nine patients admitted to ITU/HDU over a 9-year period (1996-2004) with severe acute pancreatitis were reviewed. There were 109 admissions to the ITU with length of stay of 0.2-81.6 days (mean 19.7 days) and 92 admissions to the HDU with length of stay of 0.4-12.8 days (mean 4.9 days). RESULTS: One hundred and seventy-nine computed tomography (CT) and 199 ultrasound (US) examinations were performed on the ITU patients in whom interventional procedures were required in 24% of patients undergoing CT examinations and in 32% of patients undergoing US. Sixty-two CT and 60 US examinations were performed in the HDU patients. The percentage of interventional procedures performed in HDU patients was similar to that in ITU patients, i.e., 18% CT-guided and 35% US-guided. The proportion of patients that underwent investigations and interventions has gradually increased over the period of the study. Inpatient mortalities were 29% and 5.4%, respectively, in ITU and HDU patients. CONCLUSIONS: This study demonstrates the huge input and increasing workload undertaken by radiologists when managing patients with severe acute pancreatitis in an ITU/HDU setting. We believe this is partly due to the implementation of the British Society of Gastroenterology (BSG) guidelines on management of acute pancreatitis and partly due to the more intensive non-surgical management offered to patients being referred into a specialist tertiary referral unit.