A 3-year EU-funded project (EUCALB), initially involving 14 countries and more than 30 scientists and physicians, was undertaken with the main objective of identifying practical risk assessment criteria for Lyme borreliosis. A major part of the project was dedicated to the improvement of data quality. European case definitions were formulated and quality assurance schemes were developed for serological diagnosis and the detection of infection in ticks. Studies on the standardisation of immunoblot interpretation criteria are still in progress. Data on the clinical risk from tick bites were obtained and considerable progress was made in elucidating the complex ecology of the disease. A study on habitat assessment throughout Europe concluded that high risk was associated with highly heterogeneous recreational woodland and case data from both high and low incidence countries suggested that most infections were acquired in recreational areas. Considerable work is still required to relate clinical data to the epidemiology and ecology of the disease in order to assess risk in Lyme borreliosis.

Animals↗

PubMed1999

No evidence for association of multiple sclerosis with the complement factors C6 and C7.

Four genome screens in multiple sclerosis have been completed and each has identified evidence for linkage in the pericentromeric region of chromosome 5. This region encodes a number of candidate genes including those for the complement components C6, C7 and C9. We have used a multiplexed oligoligation assay (OLA) to test single nucleotide polymorphisms (SNPs) from the C6 and C7 genes for evidence of association with multiple sclerosis in our sibling pair families. There was no statistically significant difference in the allele frequencies of these polymorphisms in the index cases from our families when compared with locally derived controls. No evidence for transmission distortion was seen with any of the polymorphisms, or with the haplotype built from the three SNPs from the C7 gene. Despite offering themselves as potential candidates these complement genes appear not to confer susceptibility to multiple sclerosis.

Autoimmune Diseases↗

PubMed1999

A screen of candidates from peaks of linkage: evidence for the involvement of myeloperoxidase in multiple sclerosis.

We tested 11 microsatellite markers for evidence of transmission distortion in 744 trio families with multiple sclerosis. Ten of the markers lie within or near to candidate genes selected on the basis that they map within the regions of potential linkage identified in our previously reported linkage genome screen, while the eleventh is an anonymous marker which had previously shown modest evidence for transmission distortion in our sibling pair families. Only the marker related to the myeloperoxidase (MPO) gene revealed tentative evidence for linkage disequilibrium and further work on this gene is clearly needed in order to resolve the status of this region in conferring susceptibility to multiple sclerosis.

Adult↗

PubMed1999

Chromosome arm 20q gains and other genomic alterations in colorectal cancer metastatic to liver, as analyzed by comparative genomic hybridization and fluorescence in situ hybridization.

Comprehensive information about the molecular cytogenetic changes in metastases of colorectal cancer is not yet available. To define such changes in metastases, we measured relative DNA sequence copy numbers by comparative genomic hybridization (CGH). Samples from 27 liver metastases and 6 synchronous primary tumors were analyzed. An average of 9.9 aberrations per tumor was found in the metastases. Gains of chromosome arms 20q (85%), 13q (48%), 7p (44%), and 8q (44%) and losses of chromosome arms 18q (89%), 8p (59%), 1p (56%), and 18p (48%) were detected most frequently. Chromosomes 14 and 15 were lost in 26% and 30% of the metastases, respectively. No consistent differences were observed between primary tumors and synchronous metastases. Fluorescence in situ hybridization (FISH) was used for further characterization of gains of chromosome arm 20q. Touch preparations of 13 tumors that had demonstrated 20q gain with CGH were examined with FISH by use of a set of probes mapping to different parts of 20q. A probe for 20p was used as a reference. FISH showed relative gain of at least one 20q locus in 12 of the tumors. High-level gains were detected in 38% of the tumors, preferentially for probes mapping to band 20q13. Our CGH data indicate that colorectal metastases show chromosomal changes similar to those that have been reported for primary tumors. Chromosomal losses were seen at higher frequency, particularly for chromosomes 14 and 15. By FISH, we identified subregions on chromosome arm 20q that are frequently involved in DNA amplifications in colorectal cancer and that may harbor candidate proto-oncogenes.

Adult↗

PubMed1999

Exploring the dense mapping of a region of potential linkage in complex disease: an example in multiple sclerosis.

In 1996 we reported the results of a genome screen in multiple sclerosis, in which potential linkage was identified in a total of twenty regions, including the centromeric region of chromosome 5. In order to investigate the efficiency of typing dense arrays of markers in regions of potential linkage, we have typed an additional nineteen microsatellite markers from this chromosome 5 region (D5S623 - D5S428) in the same sibling pair families. The mean additional information extracted per marker typed declined with increasing map density, while inaccuracies in the mapping and the density of genotyping errors increased. Our empirical results suggest that, in linkage-based experiments, there is a limit to the benefits that are gained from typing additional markers in the same families. Increasing map density up to the 2.5-5 cM level efficiently extracts valuable extra information; however, beyond this level efficiency declines while the confounding effects of mapping and genotyping errors accumulate. We, therefore, recommend that extra markers typed in linkage studies be limited to this level of resolution. Mapping regions beyond this density should only be initiated when searching for linkage disequilibrium.

Chromosome Mapping↗

PubMed1999

Primary biliary cirrhosis once rare, now common in the United Kingdom?

There is a widespread impression that the number of patients with the autoimmune liver disease primary biliary cirrhosis (PBC) is increasing, although its incidence and prevalence vary widely. Using thorough case-finding methods and rigorous definitions to assess changes in incidence and prevalence with time and to explore the symptomatology and mortality of the disease in a large group of unselected patients, we performed a descriptive epidemiological study of PBC in a well defined population over a fixed period of time using established diagnostic criteria and with clinical follow-up of all cases. In a population of 2.05 million in northern England 770 definite or probable PBC cases were identified. Prevalence rose from 201.9 per 10(6) in the adult population and 541. 4 per 10(6) women over 40 in 1987 to 334.6 per 10(6) adults and 939. 8 per 10(6) women over 40 in 1994. Incidence was 23 per 10(6) in 1987 and 32.2 per 10(6) in 1994. Three hundred patients died in median follow-up of 6.27 years (141 liver deaths); the standardized mortality ratio was 2.85. At presumed diagnosis, 60.9% had no symptoms of liver disease. By June 1994 62% of prevalent patients had liver symptoms. PBC is apparently increasing. It is still unclear whether this is because of a true increase, case finding, or increased disease awareness. The study draws attention to (1) high mortality from liver disease and non-liver-related causes even in patients initially with no liver symptoms and (2) apparently poor diagnostic awareness of the disease.

Adult↗

PubMed1999

Evidence that allelic variants of the spinocerebellar ataxia type 2 gene influence susceptibility to multiple sclerosis.

Expanded CAG trinucleotide repeats are known to be responsible for five of the autosomal dominant spinocerebellar ataxias (SCA1, SCA2, SCA3, SCA6, and SCA7). We have typed each of these repeats in 226 multiple sclerosis sibling pair families. No expanded repeats were seen, indicating an absence of SCA phenocopies in clinically defined familial multiple sclerosis. However, transmission disequilibrium testing for these repeats demonstrated significant excess transmission of the 22 repeat length allele of the SCA2 gene (P=4. 4E-06) in multiple sclerosis patients. This observation is consistent with pleiotropic effects of the SCA2 gene, with a non-dynamic mutation/polymorphism contributing epistatically to susceptibility in multiple sclerosis.

Alleles↗

PubMed1999

Identifying patients at low risk of death from cardiac failure after operation for postinfarct ventricular tachycardia.

BACKGROUND: In unselected patients, cardiac failure accounted for most deaths after antiarrhythmic operation (ER) for postinfarction ventricular tachycardia (VT). This study aimed to determine whether patients at low risk of this outcome could be predicted from a retrospective analysis of variables from 100 consecutive ER patients. METHODS: Thirteen variables suggested by other researchers as predictive of outcome were analyzed. At the time of study, ER was the only therapy available for drug refractory VT. RESULTS: Only emergency ER, wall motion score less than 3 and Killip classification were significantly related to death from cardiac failure. The lack of correlation between emergency ER and variables of ER timing, VT less than 24 hours of ER or VT type implies that the need for emergency ER is also related to ventricular dysfunction. Multivariate analysis identified a group at particularly low risk of death with a specificity of 95%. CONCLUSIONS: Patients at low risk of death after ER can be identified prospectively. In the implantable cardioverter defibrillator era, elective ER is best reserved for such patients. Emergency ER may still be justified in younger patients without comorbidity who will die of VT without it.

Adolescent↗

PubMed1999

Assessment of once-daily eprosartan, an angiotensin II antagonist, in patients with systemic hypertension. Eprosartan Study Group.

A multicenter, randomized, double-masked, placebo-controlled trial was conducted to assess the efficacy of once-daily eprosartan, a nonbiphenyl, nontetrazole angiotensin II-receptor antagonist, in 243 patients with mild-to-moderate systemic hypertension (sitting diastolic blood pressure [SitDBP], 95-114 mm Hg). After a 3-to 5-week single-masked placebo run-in period to obtain baseline values, patients were randomly allocated to receive 600 mg eprosartan once daily or placebo for 8 weeks. All clinic blood pressure measurements were made 24 hours +/-90 minutes after dosing. Eprosartan produced statistically and clinically significant reductions in SitDBP(-7.5+/-0.8 mm Hg) and sitting systolic blood pressure (SitSBP) (-6.0+/-1.3 mm Hg) compared with placebo (SitDBP -1.9+/-0.7 mm Hg; SitSBP 0.8+/-1.2 mm Hg). The 95% confidence intervals for the difference from placebo were -8.1 to 4.1 for SitDBP and -11.0 to -4.0 for SitSBP (both, P<0.0001). The proportion of patients responding (SitDBP was <90 mm Hg or had decreased by > or =10 mm Hg from baseline at study end point) to eprosartan was significantly higher than the proportion of those responding to placebo (42% vs. 21%, respectively; P = 0.0003). Similar results were obtained in a subgroup analysis comparing patients aged <65 years with those aged > or =65 years. The total number of adverse events was similar in the eprosartan and placebo groups. Eprosartan 600 mg once daily was both well tolerated and effective, providing significant blood pressure reduction 24 hours after dosing in patients with mild-to-moderate systemic hypertension, regardless of age.

Acrylates↗

PubMed1999

An outbreak of Bacillus cereus respiratory tract infections on a neonatal unit due to contaminated ventilator circuits.

An outbreak of Bacillus cereus respiratory tract infections affecting six ventilated preterm neonates over a two-week period is described. Reusable ventilator circuits were identified as the cause of the outbreak. Ordinarily these were reprocessed on the Neonatal Unit (NNU), first through a washing machine and then through a low-temperature steam (LTS) disinfector. The onset of the outbreak coincided with a breakdown of the LTS facility, which necessitated sending the washed circuits off site for LTS disinfection. The washing machine was shown to be contaminated with the same serovars of B. cereus as those isolated from patients. Two critical steps in the off site LTS disinfection process allowed exsporulation and multiplication of B. cereus: the circuits were inadequately dried after processing, whilst return of the moist circuits to the NNU was often delayed. The outbreak was terminated by withdrawal of the heat-disinfected ventilator circuits. This outbreak emphasizes the need for high standards where medical equipment is reprocessed, especially for use in vulnerable patients.

Bacillaceae Infections↗

PubMed1999

Breast cancer cell-associated endopeptidase EC 24.11 modulates proliferative response to bombesin.

We have investigated the production, growth and inactivation of gastrin-releasing peptide (GRP)-like peptides in human breast cancer cell lines. Radioimmunoassay detected GRP-like immunoreactivity (GRP-LI) in T47D breast cancer cells but not in the conditioned medium, indicating rapid clearance. No GRP-LI was found in the ZR-75-1 or MDA-MB-436 cells or their conditioned medium. High-performance liquid chromatography (HPLC) analysis of the GRP-LI in the T47D cells revealed a major peak, which co-eluted with GRP(18-27), and a minor more hydrophilic peak. In vitro stimulation of T47D cell growth by bombesin (BN) was enhanced to 138% of control levels (bombesin alone) by the addition of the selective endopeptidase EC 3.4.24.11 inhibitor phosphoramidon (0.1 ng ml(-1)). Fluorogenic analysis using whole cells confirmed low levels of this phosphoramidon-sensitive enzyme on the T47D cells. This enzyme, previously unreported in human breast cancer cells, significantly modulates both T47D growth and its response to BN-induced growth.

Bombesin↗

PubMed1999

More evidence that founder effects exist in the European population.

Explore the source record for details and available documents.

Alleles↗

PubMed1999

The subjective effects of smoking on nasal symptoms.

One hundred and forty-four volunteers completed a validated questionnaire, to investigate the association between smoking, non-smoking and passive smoking status, and the degree of a range of 10 common nasal symptoms. Logistic regression showed that smokers were four times and passive smokers six times more likely to report hyposmia compared to non-smokers. No significant differences were found between the three groups for any of the other nine symptoms.

Adolescent↗

PubMed1999

Quality procedures in non-gynaecological cytology laboratories in England and Wales.

All non-gynaecological cytology laboratories in England and Wales (n = 212) were surveyed by telephone. The aim was to investigate what concepts of quality applied in this context and to establish what tools and techniques of quality improvement were used. The overall response was 146 (69%). The respondents mainly comprised NHS Trusts and University Departments. The study showed that there was a diverse approach to quality. All types of quality assurance and customer focus procedure questioned were undertaken but to a varied extent; three laboratories (2%) used a complete range and three (2%) used no procedure at all. Accreditation was associated with staffing adequacy and use of surveys, but not quality assurance (QA) or user focus. Laboratories with a high priority for quality performed more QA and reported a higher staffing adequacy. Critical incident analysis was dependent on workload. Computerization did not affect quality procedures and involvement in the Breast Screening Programme did not result in different quality measures. The time since last update was independent of all factors and external quality assurance (EQA) was not widely available. The study suggested that an integrated approach to quality had not been adopted in English and Welsh cytology laboratories and that there may be a need for a more strategic approach with greater availability of EQA, guidelines on quality tools, closer linkage of accreditation and quality procedures and the production of minimum and ideal standards. The ideal standard could be the complete range of procedures, and the minimum standard could comprise those processes in most frequent use, i.e. critical incident analysis, correlation methods, action on information, analysis of what is done with diagnostic information, a complaints procedure and customer surveys.

Consumer Behavior↗