The morbidity and mortality following a diagnosis of peripheral arterial disease: Long-term follow-up of a large database

BACKGROUND: Awareness of the significance of peripheral arterial disease is increasing, but quantitative estimates of the ensuing burden and the impact of other risk factors remains limited. The objective of this study was to fill this need. METHODS: Morbidity and mortality were examined in 16,440 index patients diagnosed with peripheral arterial disease in Saskatchewan, Canada between 1985 and 1995. Medical history and patient characteristics were available retrospectively to January 1980 and follow-up was complete to March 1998. Crude and adjusted event rates were calculated and Kaplan-Meier survival curves estimated. Cox proportional hazards analyses were conducted to examine the effect of risk factors on these rates. Patients suffering a myocardial infarction or ischemic stroke in Saskatchewan provided two reference populations. RESULTS: Half of the index patients were male; the majority was over age 65; 73% had at least one additional risk factor at index diagnosis; 10% suffered a subsequent stroke, another 10% a myocardial infarction, and 49% died within the mean follow-up of 5.9 years. Annual mortality (8.2%) was higher among patients with PAD than after a myocardial infarction (6.3%) but slightly lower than that in patients suffering a stroke (11.3%). Index patients with comorbid disease (e.g., diabetes) were at highest risk of death and other events. CONCLUSION: A diagnosis of peripheral arterial disease is critical evidence of more widespread atherothrombotic disease, with substantial risks of subsequent cardiovascular events and death. Given that the majority has additional comorbidities, these risks are further increased

Visualising biological data: a semantic approach to tool and database integration

<p>Abstract</p> <p>Motivation</p> <p>In the biological sciences, the need to analyse vast amounts of information has become commonplace. Such large-scale analyses often involve drawing together data from a variety of different databases, held remotely on the internet or locally on in-house servers. Supporting these tasks are <it>ad hoc </it>collections of data-manipulation tools, scripting languages and visualisation software, which are often combined in arcane ways to create cumbersome systems that have been customised for a particular purpose, and are consequently not readily adaptable to other uses. For many day-to-day bioinformatics tasks, the sizes of current databases, and the scale of the analyses necessary, now demand increasing levels of automation; nevertheless, the unique experience and intuition of human researchers is still required to interpret the end results in any meaningful biological way. Putting humans in the loop requires tools to support real-time interaction with these vast and complex data-sets. Numerous tools do exist for this purpose, but many do not have optimal interfaces, most are effectively isolated from other tools and databases owing to incompatible data formats, and many have limited real-time performance when applied to realistically large data-sets: much of the user's cognitive capacity is therefore focused on controlling the software and manipulating esoteric file formats rather than on performing the research.</p> <p>Methods</p> <p>To confront these issues, harnessing expertise in human-computer interaction (HCI), high-performance rendering and distributed systems, and guided by bioinformaticians and end-user biologists, we are building reusable software components that, together, create a toolkit that is both architecturally sound from a computing point of view, and addresses both user and developer requirements. Key to the system's usability is its direct exploitation of semantics, which, crucially, gives individual components knowledge of their own functionality and allows them to interoperate seamlessly, removing many of the existing barriers and bottlenecks from standard bioinformatics tasks.</p> <p>Results</p> <p>The toolkit, named Utopia, is freely available from <url>http://utopia.cs.man.ac.uk/</url>.</p

The Mitochondrial Genome of the Legume Vigna radiata and the Analysis of Recombination across Short Mitochondrial Repeats

The mitochondrial genomes of seed plants are exceptionally fluid in size, structure, and sequence content, with the accumulation and activity of repetitive sequences underlying much of this variation. We report the first fully sequenced mitochondrial genome of a legume, Vigna radiata (mung bean), and show that despite its unexceptional size (401,262 nt), the genome is unusually depauperate in repetitive DNA and "promiscuous" sequences from the chloroplast and nuclear genomes. Although Vigna lacks the large, recombinationally active repeats typical of most other seed plants, a PCR survey of its modest repertoire of short (38–297 nt) repeats nevertheless revealed evidence for recombination across all of them. A set of novel control assays showed, however, that these results could instead reflect, in part or entirely, artifacts of PCR-mediated recombination. Consequently, we recommend that other methods, especially high-depth genome sequencing, be used instead of PCR to infer patterns of plant mitochondrial recombination. The average-sized but repeat- and feature-poor mitochondrial genome of Vigna makes it ever more difficult to generalize about the factors shaping the size and sequence content of plant mitochondrial genomes

The Global Diversity of Parasitic Isopods Associated with Crustacean Hosts (Isopoda: Bopyroidea and Cryptoniscoidea)

Parasitic isopods of Bopyroidea and Cryptoniscoidea (commonly referred to as epicarideans) are unique in using crustaceans as both intermediate and definitive hosts. In total, 795 epicarideans are known, representing ∼7.7% of described isopods. The rate of description of parasitic species has not matched that of free-living isopods and this disparity will likely continue due to the more cryptic nature of these parasites. Distribution patterns of epicarideans are influenced by a combination of their definitive (both benthic and pelagic species) and intermediate (pelagic copepod) host distributions, although host specificity is poorly known for most species. Among epicarideans, nearly all species in Bopyroidea are ectoparasitic on decapod hosts. Bopyrids are the most diverse taxon (605 species), with their highest diversity in the North West Pacific (139 species), East Asian Sea (120 species), and Central Indian Ocean (44 species). The diversity patterns of Cryptoniscoidea (99 species, endoparasites of a diverse assemblage of crustacean hosts) are distinct from bopyrids, with the greatest diversity of cryptoniscoids in the North East Atlantic (18 species) followed by the Antarctic, Mediterranean, and Arctic regions (13, 12, and 8 species, respectively). Dajidae (54 species, ectoparasites of shrimp, mysids, and euphausids) exhibits highest diversity in the Antarctic (7 species) with 14 species in the Arctic and North East Atlantic regions combined. Entoniscidae (37 species, endoparasites within anomuran, brachyuran and shrimp hosts) show highest diversity in the North West Pacific (10 species) and North East Atlantic (8 species). Most epicarideans are known from relatively shallow waters, although some bopyrids are known from depths below 4000 m. Lack of parasitic groups in certain geographic areas is likely a sampling artifact and we predict that the Central Indian Ocean and East Asian Sea (in particular, the Indo-Malay-Philippines Archipelago) hold a wealth of undescribed species, reflecting our knowledge of host diversity patterns

Solution structure of a repeated unit of the ABA-1 nematode polyprotein allergen of ascaris reveals a novel fold and two discrete lipid-binding sites

Parasitic nematode worms cause serious health problems in humans and other animals. They can induce allergic-type immune responses, which can be harmful but may at the same time protect against the infections. Allergens are proteins that trigger allergic reactions and these parasites produce a type that is confined to nematodes, the nematode polyprotein allergens (NPAs). These are synthesized as large precursor proteins comprising repeating units of similar amino acid sequence that are subsequently cleaved into multiple copies of the allergen protein. NPAs bind small lipids such as fatty acids and retinol (Vitamin A) and probably transport these sensitive and insoluble compounds between the tissues of the worms. Nematodes cannot synthesize these lipids, so NPAs may also be crucial for extracting nutrients from their hosts. They may also be involved in altering immune responses by controlling the lipids by which the immune and inflammatory cells communicate. We describe the molecular structure of one unit of an NPA, the well-known ABA-1 allergen of Ascaris and find its structure to be of a type not previously found for lipid-binding proteins, and we describe the unusual sites where lipids bind within this structur

Alcohol, metabolic risk and elevated serum gamma-glutamyl transferase (GGT) in Indigenous Australians

<p>Abstract</p> <p>Background</p> <p>The interaction between overweight/obesity and alcohol intake on liver enzyme concentrations have been demonstrated. No studies have yet examined the interaction between metabolic syndrome or multiple metabolic risk factors and alcohol intake on liver enzymes. The aim of this study was to examine if alcohol consumption modifies the effect of metabolic risk on elevated serum GGT in Indigenous Australians.</p> <p>Methods</p> <p>Data were from N = 2609 Indigenous Australians who participated in a health screening program in rural far north Queensland in 1999-2000 (44.5% response rate). The individual and interactive effects of metabolic risk and alcohol drinking on elevated serum GGT concentrations (≥50 U/L) were analyzed using logistic regression.</p> <p>Results</p> <p>Overall, 26% of the population had GGT≥50 U/L. Elevated GGT was associated with alcohol drinking (moderate drinking: OR 2.3 [95%CI 1.6 - 3.2]; risky drinking: OR 6.0 [4.4 - 8.2]), and with abdominal obesity (OR 3.7 [2.5 - 5.6]), adverse metabolic risk cluster profile (OR 3.4 [2.6 - 4.3]) and metabolic syndrome (OR 2.7 [2.1 - 3.5]) after adjustment for age, sex, ethnicity, smoking, physical activity and BMI. The associations of obesity and metabolic syndrome with elevated GGT were similar across alcohol drinking strata, but the association of an adverse metabolic risk cluster profile with elevated GGT was larger in risky drinkers (OR 4.9 [3.7 - 6.7]) than in moderate drinkers (OR 2.8 [1.6 - 4.9]) and abstainers (OR 1.6 [0.9 - 2.8]).</p> <p>Conclusions</p> <p>In this Indigenous population, an adverse metabolic profile conferred three times the risk of elevated GGT in risky drinkers compared with abstainers, independent of sex and ethnicity. Community interventions need to target both determinants of the population's metabolic status and alcohol consumption to reduce the risk of elevated GGT.</p

Unusual cardiovascular complications of brucellosis presenting in two men: two case reports and a review of the literature

Introduction: Brucellosis is a zoonosis with worldwide distribution, which is particularly endemic in many countries of the Mediterranean basin. Cardiovascular complications of this disease, such as endocarditis, myocarditis and pericarditis, are very rare, with even fewer cases of myocarditis or asymptomatic pericardial effusion in the absence of concomitant endocarditis being reported. Case presentation: We report two cases of brucellosis in two Caucasian men, aged 17 and 34 years old, with myocarditis and asymptomatic pericardial effusion, respectively. Of note, neither patient had concomitant endocarditis. The disease was confirmed serologically and by blood cultures. Both patients recovered completely after receiving appropriate antibiotic treatment without any sign of relapse during a follow-up of 12 months. Conclusion: These two cases emphasize that in endemic areas Brucella can be considered as a potentially causative agent of idiopathic pericardial effusion or myocarditis, even in the absence of concomitant endocarditis. This possibility could be taken into account particularly in cases where contraction of brucellosis is possible, such as occupational exposure or consumption of unpasteurized dairy products. © 2011 Gatselis et al; licensee BioMed Central Ltd

Health-seeking behaviour of human brucellosis cases in rural Tanzania

<p>Abstract</p> <p>Background</p> <p>Brucellosis is known to cause debilitating conditions if not promptly treated. In some rural areas of Tanzania however, practitioners give evidence of seeing brucellosis cases with symptoms of long duration. The purpose of this study was to establish health-seeking behaviour of human brucellosis cases in rural Tanzania and explore the most feasible ways to improve it.</p> <p>Methods</p> <p>This was designed as a longitudinal study. Socio-demographic, clinical and laboratory data were collected from patients who reported to selected hospitals in rural northern Tanzania between June 2002 and April 2003. All patients with conditions suspicious of brucellosis on the basis of preliminary clinical examination and history were enrolled into the study as brucellosis suspects. Blood samples were taken and tested for brucellosis using the Rose-Bengal Plate Test (RBPT) and other agglutination tests available at the health facilities and the competitive ELISA (c-ELISA) test at the Veterinary Laboratory Agencies (VLA) in the UK. All suspects who tested positive with the c-ELISA test were regarded as brucellosis cases. A follow-up of 49 cases was made to collect data on health-seeking behaviour of human brucellosis cases.</p> <p>Results</p> <p>The majority of cases 87.7% gave a history of going to hospital as the first point of care, 10.2% purchased drugs from a nearby drug shop before going to hospital and 2% went to a local traditional healer first. Brucellosis cases delayed going to hospital with a median delay time of 90 days, and with 20% of the cases presenting to hospitals more than a year after the onset of symptoms. Distance to the hospital, keeping animals and knowledge of brucellosis were significantly associated with patient delay to present to hospital.</p> <p>Conclusion</p> <p>More efforts need to be put on improving the accessibility of health facilities to the rural poor people who succumb to most of the diseases including zoonoses. Health education on brucellosis in Tanzania should also stress the importance of early presentation to hospitals for prompt treatment.</p

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al