Compliance-Adjusted Estimates of Aspirin Effects Among Older Persons in the ASPREE Randomized Trial.

The Aspirin in Reducing Events in the Elderly (ASPREE) Trial recruited 19,114 participants across Australia and the United States during 2010-2014. Participants were randomized to receive either 100 mg of aspirin daily or matching placebo, with disability-free survival as the primary outcome. During a median 4.7 years of follow-up, 37% of participants in the aspirin group permanently ceased taking their study medication and 10% commenced open-label aspirin use. In the placebo group, 35% and 11% ceased using study medication and commenced open-label aspirin use, respectively. In order to estimate compliance-adjusted effects of aspirin, we applied rank-preserving structural failure time models. The results for disability-free survival and most secondary endpoints were similar in intention-to-treat and compliance-adjusted analyses. For major hemorrhage, cancer mortality, and all-cause mortality, compliance-adjusted effects of aspirin indicated greater risks than were seen in intention-to-treat analyses. These findings were robust in a range of sensitivity analyses. In accordance with the original trial analyses, compliance-adjusted results showed an absence of benefit with aspirin for primary prevention in older people, along with an elevated risk of clinically significant bleeding.

Sex hormones, SHBG and cognitive performance among older Australian women: an observational study.

OBJECTIVE: This study aims to explore the associations between sex hormones and cognitive performance in older women. METHODS: Associations between sex hormones, sex hormone binding globulin (SHBG) and cognitive performance were examined in women aged at least 70 years, without dementia and not using medications that influence sex hormones. Linear and generalized linear regression models included age, body mass index, education, smoking, alcohol, living circumstances, diabetes, hypertension, depression and impaired renal function. RESULTS: The included 5511 women had a median (interquartile range) age of 73.9 (71.6-77.6) years. No associations were found for estrone, estradiol, testosterone or dehydroepiandrosterone and cognitive performance. SHBG concentrations above quartile 1 (Q1) were significantly inversely associated with processing speed (Q2, ß = -0.94, 95% confidence interval [CI] - 1.64 to -0.24, p = 0.009; Q3, ß = -0.82, 95% CI -1.53 to -0.10, p = 0.025; and Q4, ß = -0.95, 95% CI -1.70 to -0.20, p = 0.013). CONCLUSIONS: Sex hormones were not associated with cognitive performance. The finding that low SHBG is associated with better processing speed warrants further investigation. The null findings for the sex hormones establish a firm baseline to confidently explore the association between sex hormones and longitudinal cognitive performance in this population. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number Register (ISRCTN83772183) and ClinicalTrials.gov (NCT01038583).

Shaped-bolus protocol reduces contrast medium volume in abdominal CT while maintaining image quality.

AIM: To prospectively assess whether bolus shaping to exponentially decrease the contrast medium injection rate leads to alteration in image validity or renal function. MATERIALS AND METHODS: In this prospective study, patients alternatively received 100 ml contrast medium versus 75 ml via bolus shaping. Image quality was assessed via measurement of attenuation values in the aorta, liver, and spleen and also blinded subjective assessment of image sharpness, low contrast detectability, image noise, and overall quality. Renal function was assessed by change in creatinine levels up to 72 hours post-contrast medium administration. RESULTS: Of 190 abdominal computed tomography (CT) studies performed in the 3-month period, 98 received the 75 ml dose. There was no significant difference in renal function or objective image quality with a significant improvement in image sharpness in the 100 ml group. CONCLUSIONS: By using bolus-shaping software, it is possible to maintain objective image quality while reducing the contrast medium load to the patient. This has significant implications regarding clinical practice in decreasing cost and risks associated with iodinated contrast media.

ASPREE-D: Aspirin for the prevention of depression in the elderly.

BACKGROUND: Not only is depression associated with increased inflammation but inflammation is a risk factor for the genesis of depression. Many of the environmental risk factors for depression are transduced through inflammatory signaling. Anti-inflammatory agents show promise for the management of depression in preclinical, epidemiological, and early clinical studies. This opens the door to the potential for anti-inflammatory agents to treat and prevent depression. There are no evidence-based pharmacotherapies for depression prevention. METHOD: ASPREE-D, aspirin in the prevention of depression in the elderly, is a sub study of ASPREE, which explores the potential of aspirin to prevent a range of inflammation related disorders in the elderly. With a sample size of 19,114, and a duration of 5 years, this placebo controlled study will be one of the largest randomized controlled trials in psychiatry and will provide definitive evidence on the ability of aspirin to prevent depression. RESULTS: This paper presents the rationale for the study and presents a summary of the study design. CONCLUSIONS: ASPREE-D may not only define novel therapy but will provide mechanistic proof of concept of the role of inflammation in depression.

Seventy-five-million-year-old tropical tetra-like fish from Canada tracks Cretaceous global warming.

Newly discovered fossil fish material from the Cretaceous Dinosaur Park Formation of Alberta, Canada, documents the presence of a tropical fish in this northern area about 75 million years ago (Ma). The living relatives of this fossil fish, members of the Characiformes including the piranha and neon tetras, are restricted to tropical and subtropical regions, being limited in their distribution by colder temperatures. Although characiform fossils are known from Cretaceous through to Cenozoic deposits, none has been reported previously from North America. The modern distribution of characiforms in Mexico and southern Texas in the southernmost United States is believed to have been the result of a relatively recent colonization less than 12 Ma. The new Canadian fossils document the presence of these fish in North America in the Late Cretaceous, a time of significantly warmer global temperatures than now. Global cooling after this time apparently extirpated them from the northern areas and these fishes only survived in more southern climes. The lack of early Cenozoic characiform fossils in North America suggests that marine barriers prevented recolonization during warmer times, unlike in Europe where Eocene characiform fossils occur during times of global warmth.

Postmenopausal hormone therapy and regional brain volumes: the WHIMS-MRI Study.

OBJECTIVES: To determine whether menopausal hormone therapy (HT) affects regional brain volumes, including hippocampal and frontal regions. METHODS: Brain MRI scans were obtained in a subset of 1,403 women aged 71-89 years who participated in the Women's Health Initiative Memory Study (WHIMS). WHIMS was an ancillary study to the Women's Health Initiative, which consisted of two randomized, placebo-controlled trials: 0.625 mg conjugated equine estrogens (CEE) with or without 2.5 mg medroxyprogesterone acetate (MPA) in one daily tablet. Scans were performed, on average, 3.0 years post-trial for the CEE + MPA trial and 1.4 years post-trial for the CEE-Alone trial; average on-trial follow-up intervals were 4.0 years for CEE + MPA and 5.6 years for CEE-Alone. Total brain, ventricular, hippocampal, and frontal lobe volumes, adjusted for age, clinic site, estimated intracranial volume, and dementia risk factors, were the main outcome variables. RESULTS: Compared with placebo, covariate-adjusted mean frontal lobe volume was 2.37 cm(3) lower among women assigned to HT (p = 0.004), mean hippocampal volume was slightly (0.10 cm(3)) lower (p = 0.05), and differences in total brain volume approached significance (p = 0.07). Results were similar for CEE + MPA and CEE-Alone. HT-associated reductions in hippocampal volumes were greatest in women with the lowest baseline Modified Mini-Mental State Examination scores (scores <90). CONCLUSIONS: Conjugated equine estrogens with or without MPA are associated with greater brain atrophy among women aged 65 years and older; however, the adverse effects are most evident in women experiencing cognitive deficits before initiating hormone therapy.

Cognitive impairment in hemodialysis patients is common.

BACKGROUND: Hemodialysis patients are at high risk for cognitive impairment due to their older age and high prevalence of stroke and cardiovascular risk factors. METHODS: Using a cross-sectional design, the authors measured cognitive function in 374 hemodialysis patients aged 55 years and older and an age-matched comparison group in Minneapolis and St. Paul, MN. Cognitive performance was measured in three domains: memory, executive function, and language. Subjects were classified as having no, mild, moderate, or severe cognitive impairment. RESULTS: Of 338 subjects who completed testing in at least two of the three cognitive domains, 13.9% (95% CI 10.4, 18.1) were classified with mild impairment, 36.1% (31.0, 41.5) with moderate impairment, 37.3% (32.1, 42.7) with severe impairment, and 12.7% (9.4, 16.8) with normal cognition. Only 2.9% had a documented history of cognitive impairment. Factors associated with severe cognitive impairment on adjusted logistic regression were stroke (adjusted OR [AOR] 1.95; 95% CI 1.08, 3.49; p < 0.03), equilibrated Kt/V > 1.2 (1.67; 1.01, 2.75; p < 0.05), and education >12 years (0.32; 0.14, 0.72; p < 0.01). The AOR for severe cognitive impairment in a random sample of 101 hemodialysis patients vs an age-matched comparison group was 3.54 (1.28, 9.78; p < 0.02). CONCLUSIONS: Moderate to severe cognitive impairment is common and undiagnosed in hemodialysis patients. Further studies are needed to determine whether dialysis exacerbates the cognitive impairment attributable to underlying disease. Cognitive testing in hemodialysis patients before dialysis initiation and periodically may be warranted.

How to ... place a lower bonded retainer.

Post-orthodontic relapse of lower incisors is a common phenomenon. Sometimes a bonded retainer is fitted to prevent this relapse. In this article, we suggest a handy clinical technique of fitting a lower bonded retainer, which is convenient and easy to carry out.

How to avoid common errors in clinical photography.

This paper demonstrates some of the errors commonly seen in both conventional and digital photography when used for clinical purposes, and details how some of these mistakes may be avoided.

Antimicrobial resistance in E.coli associated with urinary tract infection in the west of Ireland.

BACKGROUND: Knowledge of antimicrobial resistance patterns in E. coli, the predominant pathogen associated with urinary tract infection (UTI) is important as a guide in selecting empirical antimicrobial therapy AIMS: To describe the antimicrobial susceptibility of E. coli associated with UTI in a region in the West of Ireland. METHODS: A collection of 934 E. coli isolates associated with UTI were tested for susceptibility to a panel of antimicrobial agents by the disc diffusion method of the National Committee for Clinical Laboratory Standards. RESULTS: More than 50% of E. coli were resistant to ampicillin, more than 40% resistant to sulphonamide and more than 30% resistant to trimethoprim. From 7.9% (community) to 12.5% (hospital) are resistant to co-amoxiclav with approximately 20% of isolates of intermediate susceptibility. In general practice most E. coli remain susceptible to nitrofurantoin (96.7%), nalidixic acid (93.9%) and ciprofloxacin (94.7%). For all agents rates of resistance were higher in hospital as compared with general practice isolates. Three isolates with the phenotype of Extended Spectrum Beta-lactamase (ESBL) resistance were detected. CONCLUSIONS: Ampicillin/amoxicillin are not suitable for empiric therapy of UTI in general practice or hospital patients in this region. There is doubt as to the role of trimethorpim or co-trimoxazole for empiric therapy of UTI. Nitrofurantoin, nalidixic acid and ciprofloxacin are active against the great majority of UTI associated E. coli.

Digital records in orthodontics.

In this electronic age there is a general move towards keeping digital records, and many trades and professions now use digital images exclusively. In this article, the advantages (and occasional disadvantages) of the use of digital photography, digital radiography and the latest development--digital study models--in orthodontics are discussed.

Evaluation of a PCR/DNA probe colorimetric membrane assay for identification of Campylobacter spp. in human stool specimens.

DNA was extracted from 50 human stool specimens using the QIAamp DNA stool minikit. PCR amplification was followed by post-PCR hybridization to DNA probes specific for the Campylobacter genus, Campylobacter jejuni, and Campylobacter coli in a colorimetric membrane assay. Thirty-two of 38 culture-positive specimens were PCR/DNA probe positive for C. jejuni. The assay is rapid and simple and can be applied to stool specimens for the detection of Campylobacter.

The oldest fossil cichlids (Teleostei: Perciformes): indication of a 45 million-year-old species flock.

Five closely related species of fossil cichlids collected from an Eocene site in Tanzania, East Africa, represent the oldest known cichlids. The specimens are whole-body, articulated fishes that are extremely well preserved and, therefore, have the potential to add to our knowledge of the history of this family. Modern cichlids are particularly well known for the numerous species flocks of the East African Great Lakes. A great deal of research is ongoing regarding all aspects of the fishes in these flocks, including their evolutionary history The new collection of fossils reported here is interpreted as representing a species flock that arose in a small crater lake. These fossils indicate that cichlids' ability to form species flocks evolved early in the history of this family.

The teaching of occupational and environmental medicine to medical students in Australia and New Zealand.

All the medical schools in Australia and New Zealand were surveyed in order to determine the amount of teaching devoted to occupational and environmental medicine in the medical courses in 1998. A 100% response rate was achieved. The results showed that the number of hours devoted to these topics varied widely, but averaged 12.8 h and 10.5 topics. The most significant factor accounting for the variability was the presence on the universities' teaching staff of individuals trained in the practice of occupational medicine. While our findings show a greater time devoted to these topics than those of similar studies in the United States and Britain, the absolute time remains small when compared with the prevalence of occupational medicine problems in the community. There is little congruence in terms of both content and assessment processes between schools.

For four sixes.

This article reviews the literature on orthodontic treatment involving extraction of first molars and highlights many of the clinical considerations when treating such cases. Case reports illustrate the potential problems and indicate some solutions.

Acyltransferase activities in the yolk sac membrane of the chick embryo.

The activities of some enzymes of glycerolipid synthesis and fatty acid oxidation were measured in subcellular fractions of the yolk sac membrane (YSM), an extra-embryonic tissue that mediates the transfer of lipid from the yolk to the circulation of the chick embryo. The activities of monoacylglycerol acyltransferase and carnitine palmitoyl transferase-1 in the YSM (respectively, 284.8+/-13.2 nmol/min/mg microsomal protein and 145.6+/-9.1 nmol/min/mg mitochondrial protein; mean +/- SE; n = 4) at day 12 of development appear to be the highest yet reported for any animal tissue. Also, the carnitine palmitoyl transferase-1 of the YSM was very insensitive to inhibition by malonyl CoA. The maximal activities of glycerol-3-phosphate acyltransferase and diacylglycerol acyltransferase in the YSM (respectively, 26.7+/-2.2 and 36.1+/-2.1 nmol/min/mg microsomal protein) were also high compared with the reported values for various animal tissues. The very high enzymic capacity for glycerolipid synthesis supports the hypothesis that the yolk-derived lipids are subjected to hydrolysis followed by reesterification during transit across the YSM. The monoacylglycerol pathway appears to be the main route for glycerolipid resynthesis in the YSM. The results also suggest that the YSM has the capacity to perform simultaneously beta-oxidation at a high rate in order to provide energy for the lipid transfer process.

Piggyback archwires.

Commonly, clinicians' principal tool in the alignment phase of orthodontic mechanotherapy is the nickel-titanium wire. During the course of orthodontic treatment, however, there are times when some segments of the dental arch require flexible wires, while the rest would benefit from rigid wires. In this report, we describe a technique where both of these needs are satisfied simultaneously. Specifically, a segment of nickel-titanium wire is piggybacked onto a stainless steel wire in regions where flexibility is desired. This method eliminates the problems associated with the activation, de-activation forces created along a continuous archwire and might be more economical. Clinical pictures illustrate the point.

Differential effects of haloperidol and clozapine on ionotropic glutamate receptors in rats.

Despite multiple lines of investigation the effect of neuroleptics on glutamate-mediated neurotransmission remains controversial. To study the effects of typical and atypical neuroleptics on selected parameters of glutamate-mediated neurotransmission, male Sprague-Dawley rats were randomly assigned to a 21-day oral treatment course with vehicle, haloperidol (HDL), or clozapine (CLZ). Coronal slices of rat brain were then incubated with tritiated ligands to measure NMDA, AMPA, and kainate receptor, and glutamate reuptake site density. Regions of interest included the frontal cortex, anterior cingulate cortex, dorsal striatum, ventral striatum, and the nucleus accumbens. CLZ increased the density of AMPA receptors significantly in the frontal and anterior cingulate cortices compared with normal controls. In the dorsal and ventral striatum, and nucleus accumbens as a whole, CLZ-treated rats had a higher AMPA receptor density compared with both the HDL- and vehicle-treated controls. Additionally, within the nucleus accumbens, CLZ-treated rats had a higher density of AMPA receptors compared with the HDL group in the core, and at trend level in the shell. There was a group by region interaction for NMDA receptor density, primarily reflecting the tendency of HDL treated rats to have high receptor densities in the frontal and anterior cingulate cortices. Kainate receptors and glutamate reuptake site densities did not differ significantly across groups. These results suggest a critical role for glutamate in the mediation of atypical antipsychotic drug action in anatomically-specific regions, and further encourage the investigation of glutamate neurotransmitter systems in schizophrenia.

Production of glutathione-coated microtitre plates for capturing recombinant glutathione S-transferase fusion proteins as antigens in immunoassays.

Glutathione S-transferase (GST) is commonly used as a fusion partner in producing recombinant proteins and this technology is increasingly being used to produce antigens for use in immunoassays to measure antibodies. To circumvent the requirement to purify such antigens before use, we developed a method for coupling glutathione to microtitre plates so that GST-containing recombinant proteins could be purified and immobilised in one step in a suitable state for immunoassays. This procedure involves covalent linkage (using the heterobifunctional cross-linker sulphosuccinimidyl 4-(p-maleimidophenyl)butyrate) of reduced glutathione through its sulphydryl group to lysine residues of haemoglobin previously immobilised on microtitre plates. Haemoglobin was superior over other proteins tested in giving the lowest non-specific binding; in this regard it was also important to limit the amount of cross-linker used to 0.1 mM. Using glutamic acid decarboxylase as a model antigen, the new affinity capture assay was at least as good as the two-step procedure involving direct adsorption to plates of previously purified antigen; it may have the additional advantage of preserving the antigen in a more native conformation than direct adsorption. The new assay also performed as well as an assay using anti-GST antibodies adsorbed onto plates; glutathione plates, unlike anti-GST plates, will only capture recombinant proteins containing functional GST--a significant point for some recombinant expression systems in which a large proportion of the protein product is insoluble because of incorrect folding.

Loss of dopamine D2 receptors in Alzheimer's disease with parkinsonism but not Parkinson's or Alzheimer's disease.

A significant proportion of patients with Alzheimer's disease (AD) exhibit extrapyramidal features that are referred to as parkinsonism (AD/Park) to distinguish the clinical and pathological features that differ from Parkinson's disease (PD). Previous results from this laboratory have shown that, although the presynaptic components of the dopamine (DA) system are markedly affected in AD/Park, the pathology is not similar to PD (Murray et al. 1995; Joyce et al. 1997). In the present study, we determined whether the parkinsonian symptoms in AD/Park might also reflect changes in numbers of postsynaptic DA receptors. We analyzed the binding of [125I]epidepride biding to DA D2/D3 receptors and [3H]SCH 23390 to D1 receptors by autoradiography in the striatum of six patients with PD, nine patients with AD, seven patients with AD/Park, and 14 neurologically intact control subjects. D2 receptors were reduced in the caudate and putamen of the AD/Park group (by 42 and 27% of controls, respectively) but not reduced in AD or PD. D1 receptors were elevated by 36% in the putamen of the PD group. Dopamine receptor changes are, therefore, not similar in PD, AD, and AD/Park. The elevation in D1 receptors in PD may contribute to the unwanted side effects of L-dopa treatment. The loss of D2 receptors in AD/Park, not observed in AD lacking overt parkinsonian symptomatology, may contribute to the presence of parkinsonian features and lack of responsiveness to L-dopa.