Double faecal immunochemical testing in patients with symptoms suspicious of colorectal cancer.

BACKGROUND: Faecal immunochemical test (FIT)-directed pathways based on a single test have been implemented for symptomatic patients. However, with a single test, the sensitivity is 87 per cent at 10 µg haemoglobin (Hb) per g faeces. This aims of this study were to define the diagnostic performance of a single FIT, compared with double FIT in symptomatic populations. METHODS: Two sequential prospective patient cohorts referred with symptoms from primary care were studied. Patients in cohort 1 were sent a single FIT, and those in cohort 2 received two tests in succession before investigation. All patients were investigated, regardless of having a positive or negative test (threshold 10 µg Hb per g). RESULTS: In cohort 1, 2260 patients completed one FIT and investigation. The sensitivity of single FIT was 84.1 (95 per cent c.i. 73.3 to 91.8) per cent for colorectal cancer and 67.4 (61.0 to 73.4) per cent for significant bowel pathology. In cohort 2, 3426 patients completed at least one FIT, and 2637 completed both FITs and investigation. The sensitivity of double FIT was 96.6 (90.4 to 99.3) per cent for colorectal cancer and 83.0 (77.4 to 87.8) per cent for significant bowel pathology. The second FIT resulted in a 50.0 per cent reduction in cancers missed by the first FIT, and 30.0 per cent for significant bowel pathology. Correlation between faecal Hb level was only modest (rs = 0.58), and 16.8 per cent of double tests were discordant, 11.4 per cent in patients with colorectal cancer and 18.3 per cent in those with significant bowel pathology. CONCLUSION: FIT in patients with high-risk symptoms twice in succession reduces missed significant colorectal pathology and has an acceptable workload impact.

Direct access CT for suspicion of brain tumour: an analysis of referral pathways in a population-based patient group.

BACKGROUND: Brain tumour patients see their primary care doctor on average three or more times before diagnosis, so there may be an opportunity to identify 'at risk' patients earlier. Suspecting a brain tumour diagnosis is difficult because brain tumour-related symptoms are typically non-specific. METHODS: We explored the predictive value of referral guidelines (Kernick and NICE 2005) for brain imaging where a tumour is suspected, in a population-based patient group referred for direct access CT of the head. A consensus panel reviewed whether non-tumour findings were clinically important or whether further investigation was necessary. RESULTS: Over a 5-year period, 3257 head scans were performed; 318 scans were excluded according to pre-specified criteria. 53 patients (1.8%) were reported to have intracranial tumours, of which 42 were significant (diagnostic yield of 1.43%). There were no false negative CT scans for tumour. With symptom-based referral guidelines primary care doctors can identify patients with a 3% positive predictive value (PPV). 559 patients had non-tumour findings, 31% of which were deemed clinically significant. In 34% of these 559 patients, referral for further imaging and/or specialist assessment from primary care was still thought warranted. CONCLUSION: Existing referral guidelines are insufficient to stratify patients adequately based on their symptoms, according to the likelihood that a tumour will be found on brain imaging. Identification of non-tumour findings may be significant for patients and earlier specialist input into interpretation of these images may be beneficial. Improving guidelines to better identify patients at risk of a brain tumour should be a priority, to improve speed of diagnosis, and reduce unnecessary imaging and costs. Future guidelines may incorporate groups of symptoms, clinical signs and tests to improve the predictive value.

Influences on Polish migrants' breast screening uptake in Lothian, Scotland.

OBJECTIVES: Ethnic minorities are known to have low uptake of cancer screening programmes and Polish populations to have low breast screening uptake. Breast screening uptake by women in Poland and Polish migrants to Scotland is low. We interviewed Polish women living in Lothian, Scotland, about their attitudes to breast screening. STUDY DESIGN AND METHOD: Telephone interviews were held with a sample of 11 Polish women registered with Lothian general practices and invited for breast screening in 2013 or 2014. Interviews were between November 2014 and February 2015 and were held in Polish then translated, transcribed and analysed thematically. RESULTS: Women interviewed (mean age 58 years) had lived in Scotland for an average of 7.5 years. Seven had undergone breast screening in both Poland and Scotland, three in only Scotland and one in Poland alone. Respondents usually used Scottish and Polish health systems and screening programmes in parallel. Convenience and familiarity shaped screening choices with written information neither accessed nor answering key questions e.g. about coordination between programmes. CONCLUSION: Polish women living in Scotland have difficulties in accessing screening there and often use both Polish and Scottish system. Language issues, misunderstandings about screening and different health cultures are key barriers. Combined information in Polish about all cancer screening programmes could help address low uptake.

Phosphodiesterase 4D gene, ischemic stroke, and asymptomatic carotid atherosclerosis.

BACKGROUND AND PURPOSE: Phosphodiesterase 4D (PDE4D) was identified recently as the first novel stroke gene to predispose to ischemic stroke independently of conventional risk factors. An association was only found with large vessel and cardioembolic stroke, suggesting a mechanism of accelerated atherosclerosis. We sought to replicate this association in ischemic stroke as a whole, and individual stroke subtypes, in a non-Icelandic European population. To assess a role in early atherosclerosis, we also sought associations with underlying asymptomatic atherosclerosis itself, assessed by carotid ultrasound in a community population. METHODS: A total of 737 consecutive white patients with stroke and 933 white community controls free of symptomatic cerebrovascular disease were examined using a case control methodology. For association with atherosclerosis, intima-media thickness (IMT) in a community population (n=1000) was assessed using carotid ultrasound. Nineteen single nucleotide polymorphisms (SNPs) and 1 minisatellite in the PDE4D gene were determined, with haplotyping undertaken using Phase 2.0. RESULTS: No association with ischemic stroke overall was identified. Six of the 19 SNPs were associated with cardioembolic stroke and 2 different SNPs with large vessel disease. There was no association with carotid artery IMT or carotid plaque in the asymptomatic community subjects. CONCLUSIONS: The PDE4D gene is not a major risk factor for ischemic stroke, or early atherosclerosis, within the 2 European population samples studied. On analysis of individual stroke subtypes, there is a possible association with cardioembolic stroke, but the lack of association with carotid IMT and plaque would suggest that this is via a mechanism other than accelerated atherosclerosis.

The prevalence of medical reasons for non-participation in the Scottish breast and bowel cancer screening programmes.

OBJECTIVE: Increasing uptake of cancer screening is a priority for health systems internationally, however, some patients may not attend because they are undergoing active treatment for the cancer of interest or have other medical reasons that mean participation would be inappropriate. This study aims to quantify the proportion of non-participants who have a medical reason for not attending cancer screening. METHODS: Medical reasons for not participating in breast and bowel screening were defined a priori on the basis of a literature review and expert opinion. The notes of 700 patients at two GP practices in Scotland were reviewed, to ascertain the prevalence of medical reasons amongst non-participants. Simple proportions and confidence intervals were calculated. RESULTS: 17.4% of breast and 2.3% of bowel screening non-participants had a medical reason to not participate. The two most common reasons were previous breast cancer follow up (8.86%) and recent mammogram (6.57%). CONCLUSION: These patients may not benefit from screening while also being distressed by receiving an invitation. This issue also makes accurate monitoring and target-setting for improving uptake difficult. Further work is needed to estimate robustly the extent to which medical reasons account for screening non-participation in a larger population.

Multiple enzyme restriction fragment length polymorphism analysis for high resolution distinction of Pseudomonas (sensu stricto) 16S rRNA genes.

Members of the genus Pseudomonas (sensu stricto) are important phytopathogens and agents of human infections, while other strains and species have beneficial bioremediation and biocontrol activities. Traditionally, these important species have been difficult to differentiate phenotypically; thus, rRNA lineage analyses have often been invoked. In this report, a newly developed approach is described to rapidly detect and distinguish fluorescent Pseudomonas isolates: PCR amplification of a Pseudomonas-specific 990-bp ribosomal RNA gene (rDNA) fragment [Appl. Environ. Microbiol. 64 (1998) 2545.] coupled with multiple enzyme restriction fragment length polymorphism (MERFLP) analysis using a single digestion mixture of AluI, HinfI, RsaI, and Tru9I incubated at 37 degrees C. The method distinguished 116 published sequences and 47 reference strains of authentic Pseudomonas representing 28 nomenspecies. A total of 55% (64/116) of the sequences analyzed by MERFLP were grouped into distinct phylogenetic clusters including Pseudomonas putida, P. syringae, P. aeruginosa, P. stutzeri, and P. fluorescens. The utility of the MERFLPs was confirmed when 100% (33/33) of the above named control reference strains were correctly placed into their phylogenetic clusters. The environmental relevance of the MERFLP method was confirmed when 67% of 28 forest and agricultural soil-derived presumptive Pseudomonas environmental clones and isolates were placed into the five major pseudomonad clusters, one clone fell into the P. agarici cluster, and five clones clustered near related pseudomonads. These data demonstrated that the PCR-MERFLP protocol provides an efficient and powerful tool for distinguishing isolates and rDNA gene libraries of environmental Pseudomonas species.

Carotid intima-media thickness is greater but carotid plaque prevalence is lower in black compared with white subjects.

BACKGROUND AND PURPOSE: Carotid IMT is widely used as a surrogate marker for atherosclerosis. Prospective studies in largely white populations demonstrate that it is strongly associated with carotid plaque and is an independent predictor of stroke. There are few data from black populations. In a previous study, we showed that carotid IMT is increased in black individuals in the UK. The purpose of this study was to confirm this with a larger sample size and to establish whether raised IMT in black stroke-free individuals is associated with increased carotid plaque. MATERIALS AND METHODS: High-resolution sonography was used to measure the CCA-, BIF-, and ICA-IMT and plaque in 306 black and 281 white healthy individuals recruited by random community sampling from London, U.K. Mean CCA-IMT was determined by using a semiautomated computer program that detects the blood/intima borderline and the media/adventitia borderline with the use of a gray-value algorithm. RESULTS: CCA-IMT was higher in black compared with white individuals after controlling for cardiovascular risk factors and socioeconomic status (ß = 0.050; 95%CI, 0.024-0.076; P < .001). BIF- and ICA-IMT were also increased in black subjects. In contrast, carotid plaque was more common in white individuals (OR, 2.90; 95%CI, 1.41-5.96; P = .004). CONCLUSIONS: The lack of correlation between increased IMT and carotid plaque in black individuals implies that IMT should not currently be used as a surrogate marker of atherosclerosis in black populations. It suggests that the increased IMT seen in black individuals may not represent early atherosclerosis.

The impact of a school-based nutrition education intervention on dietary intake and cognitive and attitudinal variables relating to fruits and vegetables.

OBJECTIVE: To assess the impact of a school-based nutrition education intervention aimed at increasing the consumption of fruits and vegetables. DESIGN: The intervention programme increased the provision of fruits and vegetables in schools and provided a range of point-of-purchase marketing materials, newsletters for children and parents, and teacher information. Curriculum materials at age 6-7 and 10-11 years were also developed and utilised. Evaluation was undertaken with groups of younger (aged 6-7 years) and older (aged 10-11 years) children. Methods included 3-day dietary records with interview and cognitive and attitudinal measures at baseline, with follow-up at 9 months, in intervention and control schools. SETTING: The work was undertaken in primary schools in Dundee, Scotland. SUBJECTS: Subjects comprised 511 children in two intervention schools with a further 464 children from two schools acting as controls. RESULTS: Children (n=64) in the intervention schools had an average increase in fruit intake (133+/-1.9 to 183+/-17.0 g day(-1)) that was significantly (P<0.05) greater than the increase (100+/-11.7 to 107+/-14.2 g day(-1)) estimated in children (n=65) in control schools. No other changes in food or nutrient intake were detected. Increases in scores for variables relating to knowledge about fruits and vegetables and subjective norms were also greater in the intervention than in the control group, although taste preferences for fruits and vegetables were unchanged. CONCLUSIONS: It is concluded that a whole school approach to increasing intakes of fruits and vegetables has a modest but significant effect on cognitive and attitudinal variables and on fruit intake.

A simple mini-method to extract DNA directly from soil for use with polymerase chain reaction amplification.

A rapid, simple method is used that yields amplifiable fungal and bacterial DNAs directly from soil. DNA is separated from soil contaminants by electrophoresis in low-melting-temperature agarose and used directly in polymerase chain reaction amplification. Fifty 20-mg samples can be processed in one day. Fragments of 16S and 18S ribosomal RNAs are amplified by polymerase chain reaction with DNA extracted from the soil. Universal primers are used that are capable of amplifying ribosomal DNA from a wide variety of bacteria and fungi. Eubacterial and fungal primers are used that are capable of distinguishing between eubacterial and fungal DNAs. Restriction enzyme digests are performed on amplified DNA fragments from five soil samples.

Cardiac tamponade from a fine silastic central venous catheter in a premature infant.

A 790 g infant developed cardiac tamponade 17 h after starting parenteral nutrition through a fine silastic catheter, the tip of which was accidentally positioned against the wall of the right atrium. Cold light examination suggested the diagnosis and pericardial aspiration of clear fluid with a high glucose content restored the circulation.

Transconjugation between Bacteria in the Digestive Tract of the Cutworm Peridroma saucia.

Transconjugants arising from transfer of plasmid R388::Tn1721 between donor and recipient strains of Enterobacter cloacae were detected in samples from the digestive tracts and fecal pellets of variegated cutworms (Peridroma saucia).

The cutworm Peridroma saucia (Lepidoptera: Noctuidae) supports growth and transport of pBR322-bearing bacteria.

Variegated cutworms were exposed to bean plants in microcosms sprayed with pBR322-carrying strains of Enterobacter cloacae, Klebsiella planticola, and Erwinia herbicola. The three bacterial species exhibited differential survival on leaves, in soil, and in guts and fecal pellets (frass) of the insects. High numbers of Enterobacter cloacae(pBR322) were detected in all samples, while the other species were unable to establish residence in the insect. To assess the impact of this colonization on site-to-site transport of microorganisms, larvae were fed plants that had been sprayed with the bacteria and then were transferred to uninoculated plants. Cutworms were efficient carriers of Enterobacter cloacae(pBR322), as indicated by its rapid appearance on uninoculated leaves and continued persistence in the insects for 3 days after transfer. Few Erwinia herbicola(pBR322) and K. planticola(pBR322) were obtained from larvae after transfer, although up to 10(3) CFU/g were detected in soil and on plants. Differences in bacterial survival and growth were confirmed by incubating frass overnight and observing the change in population numbers. The proportion of total samples showing at least a 25-fold increase during incubation was 68% for Enterobacter cloacae(pBR322), 39% for K. planticola(pBR322), and 0% for Erwinia herbicola(pBR322). Our results emphasize the role that cutworms and possibly other insects have in persistence and growth of microorganisms in the environment.

Prevalence of coeliac disease and longitudinal follow-up of antigliadin antibody status in children and adolescents with type 1 diabetes mellitus.

Coeliac disease (CD) is more prevalent in individuals with type 1 diabetes mellitus (DM), and when untreated is associated with a number of medical complications, including poor glycaemic control. Identification of patients with CD has been facilitated in recent years by serological screening, including the use of antigliadin antibodies (AGAs) and endomysial antibodies (EMAs). The aim of this study was to assess the prevalence of CD in a clinic-based paediatric population with type 1 DM, and to study longitudinal changes in AGA status. Two-hundred-and-eighty-one children and adolescents with type 1 DM aged 9.9 +/- 3.8 yr were screened using AGAs of immunoglobulin A (IgA) and immunoglobulin G (IgG) classes (AGA-IgA and AGA-IgG). Thirty-five patients had both antibodies positive and underwent gastro-duodenoscopy and multiple biopsies. Fifteen of the 35 patients had histological evidence of CD, and the overall clinic prevalence of CD was 5.7%. A number of patients did not exhibit florid symptoms, and recurrent unexplained hypoglycaemia was a significant finding. Patients who perceived themselves to be asymptomatic had more problems with compliance with a gluten-free diet (GFD). Ninety-seven patients had follow-up AGAs performed after 2.5 +/- 1.5 yr. One patient with initially normal AGAs developed positive antibodies and histological findings of CD. Antibody status has fluctuated in other patients. CD is common in patients with DM, and diagnosis is important to detect to minimize long-term morbidity related to both disorders. Initial normal screening does not exclude CD and repeat screening is indicated.

An effective method to extract DNA from environmental samples for polymerase chain reaction amplification and DNA fingerprint analysis.

A rapid direct-extraction method was used to obtain DNA from environmental soil samples. Heat, enzymes, and guanidine isothiocyanate were utilized to lyse cells. The DNA was purified by agarose gel electrophoresis, amplified with 16S rRNA-based primers by use of the polymerase chain reaction, and then digested with the restriction endonuclease PalI. The extraction method was used to obtain DNA from a variety of plants, bacteria, and fungi including Gossypium hirsucum (cotton), Pseudomonas, Bacillus, Streptomyces, and Colletotrichum. Up to 100 micrograms DNA/g (wet weight) of soil and 400 micrograms DNA/g of plant material were recovered. Restriction endonuclease analysis patterns of amplified rDNA from pure microbial cultures and plant species contained three to five different DNA fragments. Amplified rDNA of mixed population DNA extracts from soil samples, digested with the restriction endonuclease PalI, contained 12-20 DNA fragments, appearing as sample "fingerprints." Results from eight environmental soil samples that were analyzed suggest that the amplified rDNA fingerprints can be used to help characterize the genetic and biological diversity of the microbial populations in these samples.

Analysis of nifH gene pool complexity in soil and litter at a Douglas fir forest site in the Oregon cascade mountain range.

Nitrogen-fixing microbial populations in a Douglas fir forest on the western slope of the Oregon Cascade Mountain Range were analyzed. The complexity of the nifH gene pool (nifH is the marker gene which encodes nitrogenase reductase) was assessed by performing nested PCR with bulk DNA extracted from plant litter and soil. The restriction fragment length polymorphisms (RFLPs) of PCR products obtained from litter were reproducibly different than the RFLPs of PCR products obtained from the underlying soil. The characteristic differences were found during the entire sampling period between May and September. RFLP analyses of cloned nifH PCR products also revealed characteristic patterns for each sample type. Among 42 nifH clones obtained from a forest litter library nine different RFLP patterns were found, and among 64 nifH clones obtained from forest soil libraries 13 different patterns were found. Only two of the patterns were found in both the litter and the soil, indicating that there were major differences between the nitrogen-fixing microbial populations. A sequence analysis of clones representing the 20 distinct patterns revealed that 19 of the patterns had a proteobacterial origin. All of the nifH sequences obtained from the Douglas fir forest litter localized in a distinct phylogenetic cluster characterized by the nifH sequences of members of the genera Rhizobium, Sinorhizobium, and Azospirillum. The nifH sequences obtained from soil were found in two additional clusters, one characterized by sequences of members of the genera Bradyrhizobium, Azorhizobium, Herbaspirillum, and Thiobacillus and the other, represented by a single nifH clone, located between the gram-positive bacteria and the cyanobacteria. Our results revealed the distinctness of the nitrogen-fixing microbial populations in litter and soil in a Douglas fir forest; the differences may be related to special requirements for degradation and mineralization processes in the plant litter.

Predictive model of conjugative plasmid transfer in the rhizosphere and phyllosphere.

A computer simulation model was used to predict the dynamics of survival and conjugation of Pseudomonas cepacia (carrying the transmissible recombinant plasmid R388:Tn1721) with a nonrecombinant recipient strain in simple rhizosphere and phyllosphere microcosms. Plasmid transfer rates were derived for a mass action model, and donor and recipient survival were modeled as exponential growth and decay processes or both. Rate parameters were derived from laboratory studies in which donor and recipient strains were incubated in test tubes with a peat-vermiculite solution or on excised radish or bean leaves in petri dishes. The model predicted donor, recipient, and transconjugant populations in hourly time steps. It was tested in a microcosm planted with radish seeds and inoculated with donor and recipient strains and on leaf surfaces of radish and bean plants also growing in microcosms. Bacteria were periodically enumerated on selective media over 7 to 14 days. When donor and recipient populations were 10(6) to 10(8) CFU/g (wet weight) of plant or soil, transconjugant populations of about 10(1) to 10(4) were observed after 1 day. An initial rapid increase and a subsequent decline in numbers of transconjugants in the rhizosphere and on leaf surfaces were correctly predicted.

Increasing asthma prevalence in a rural New Zealand adolescent population: 1975-89.

A survey of asthma symptoms and spirometry in 435 adolescent schoolchildren was undertaken in 1989 in a rural, largely Maori population. The survey questionnaires were identical to those used in a 1975 survey at the same school. The prevalence of reported asthma or wheeze significantly increased from 26.2% to 34.0%. This increase occurred in groups reporting asthma, and also those reporting wheeze unassociated with colds, but without a previous diagnosis of asthma. There was a tendency for a rise in reported wheeze in Europeans (24.3% to 27.4%) and a significant rise in Maoris (27.1% to 36.2%). The reclassification of other respiratory problems did not account for the increase. Data from this study provides evidence that there has been a rise in the prevalence of asthma in this New Zealand population over a time period of 14 years.