L. Pedersen

Azathioprine, mercaptopurine and birth outcome: a population‐based cohort study

Background : Data on the safety of azathioprine and mercaptopurine during pregnancy are very sparse.

Birth outcome in women treated with azathioprine or mercaptopurine during pregnancy: A Danish nationwide cohort study.

Data on birth outcome after exposure to azathioprine or mercaptopurine during pregnancy is sparse.

Broad‐range PCR and sequencing in routine diagnosis of infective endocarditis

The aim was to evaluate “16S rDNA PCR and sequencing” (PCR) for identification of bacterial DNA in heart valves in routine diagnosis of infective endocarditis (IE). Heart valves from 74 patients with suspected infective endocarditis, and 16 controls were analysed by histology, culture and PCR. Results from blood culture served as the gold standard. Patients were classified according to the Duke criteria. The final classification resulted in 57 definitive cases of IE, 7 possible, and 10 cases without IE. Sensitivity of valve culture was 26% and specificity 62%. Sensitivity of PCR was 72% and specificity 100%. In patients who had received antibiotic treatment for less than 5 days before surgery, sensitivity of culture and PCR were comparable. In patients who had received antibiotic treatment for more than 5 days, sensitivity of valve culture was markedly reduced compared to sensitivity of PCR. In three of seven blood‐culture‐negative cases PCR was positive, including two cases with non‐cultivable bacteria. No PCR samples were contaminated, whereas 35% of valve‐culture samples were contaminated. PCR is more sensitive and specific than valve culture, and a valuable supplement to the existing analyses of valve tissue. PCR is necessary to identify the full spectrum of pathogens causing IE. In contrast to sensitivity of culture, sensitivity of PCR was independent of length of antibiotic treatment before surgery.

Highly discriminative genotyping of Chlamydia trachomatis using omp1 and a set of variable number tandem repeats

This article reports the development of a method for genotyping Chlamydia trachomatis, using PCR and sequencing of omp1, supplemented with three new variable number tandem repeat (VNTR) loci of C. trachomatis. Typeability, reproducibility and discriminatory power were assessed using four groups of samples: two groups (I and II) of C. trachomatis-positive patients and their positive partner(s), one group (III) of patients with recurrent or persistent C. trachomatis infections, and one group (IV) comprising samples containing a newly discovered mutant strain with a 377-bp deletion in the cryptic plasmid, the new variant C. trachomatis (nvCT). The VNTR loci (designated CT1335, CT1299, and CT1291) were all single nucleotide repeats chosen for maximal mutability and variation. In the study material, nine variants of CT1335, eight variants of CT1299 and five variants of CT1291 were found. The discriminatory power (D) of omp1 in the present material was D(omp1) = 0.69. Ds for VNTRs CT1335, CT1299 and CT1291 were 0.53, 0.74 and 0.74, respectively. The resolution power of the omp1-VNTR assay was 0.94. Stability over time of the VNTRs was investigated and found to be adequate for epidemiological studies. Using this genotyping assay, it was confirmed that the nvCT strain was indeed a clone. These results indicate that, with this novel method, strains of C. trachomatis can be individually identified, and epidemiological associations established.

Hormone use for menopausal symptoms and risk of breast cancer. A Danish cohort study

Numerous studies and meta-analyses have shown that hormone replacement therapy (HRT) for menopausal symptoms increases the risk of developing breast cancer, estimated to be 2.3% for each year of use. The influence of different oestrogen–progestin regimens has still not been fully evaluated. Using longitudinal data from the population-based prescription database of the county of North Jutland, Denmark, and the Danish Cancer Registry, we examined the risk of developing breast cancer in relation to HRT in a cohort of 78 380 women aged 40–67 years from 1989 to 2002. A total of 1462 cases of breast cancer were identified during a mean follow-up of 10 years. Use of HRT did not increase the risk of breast cancer in women aged 40–49 years. Restricting the cohort to 48 812 women aged 50 years or more at entry, of whom 15 631 were HRT users, we found an increased risk associated with current use of HRT (relative risk 1.61, 95% confidence interval 1.38–1.88). The risk increased with increasing duration of use and decreased with time since last HRT prescription, reaching unity after 5 years. No material risk difference was observed among the various HRT-regimens. This population-based cohort study provides further confirmation that HRT increases the risk of developing breast cancer in women aged 50 years or more.

Typing Chlamydia trachomatis : from egg yolk to nanotechnology

A historical review is provided of the various methods used for half a century to differentiate and type Chlamydia trachomatis strains. Typing of C. trachomatis is an important tool for revealing transmission patterns in sexual networks, and enabling association with clinical manifestations and pathogenicity. Serotyping using the major outer membrane protein (MOMP) has been the mainstay of epidemiological work for several decades. However, the development of nucleic acid amplification techniques (NAAT) and easy access to sequencing have shifted the focus from MOMP serotypes to omp1 genotypes. However, insufficient epidemiological resolution is achieved by characterization of both MOMP and omp1. This calls for new high-resolution genotyping methods applying for example a multilocus variable number tandem repeat assay (MLVA) or multilocus sequence typing (MLST). The futuristic nanotechnology already seems at hand to further simplify and automate the high-resolution genotyping method based on NAAT and sequencing of various targets in the C. trachomatis genome. Thereby, a high throughput can be achieved and more epidemiological information can be obtained. However, it is important to realize that culture of C. trachomatis may still be needed to detect and characterize new variants of C. trachomatis.

Eight-Plex PCR and Liquid-Array Detection of Bacterial and Viral Pathogens in Cerebrospinal Fluid from Patients with Suspected Meningitis

ABSTRACT We here report on the development of a novel multiplex PCR with product detection in a Luminex 100 suspension array system. The assay covers the nine most important bacterial and viral pathogens found in Danish meningitis patients. The microorganisms include Neisseria meningitidis, Streptococcus pneumoniae, Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, Streptococcus agalactiae, herpes simplex virus types 1 and 2, and varicella-zoster virus. The study was based on 1,187 samples, of which 55 were found to be positive by PCR. The assay was found to have an excellent sensitivity and an excellent specificity compared to the results of a “gold standard,” defined by routine laboratory tests, for the two most important pathogens, S. pneumoniae (95 and 99.1%, respectively) and N. meningitidis (100 and 99.7%, respectively). The method provides a valuable supplement to the traditional microscopy and culture of cerebrospinal fluid (CSF) samples in a routine diagnostic setting, and results can be available within 1 workday. The method is suitable for use for the initial screening and identification of nine important microorganisms in CSF samples from patients with suspected meningitis. Compared to microscopy and culture of CSF, this rapid and sensitive method will support physicians with the selection of the appropriate antimicrobial agents and the initiation of timely treatment in the absence of live microorganisms in the CSF.

Reported symptoms, diagnostic delay and stage of colorectal cancer: a population‐based study in Denmark

Objective  The primary prognostic factor for colorectal cancer (CRC) is stage. Any association between symptoms, diagnostic delay and stage may have implications for the clinical course of the disease. We examined the association between symptoms and diagnostic delay and between symptoms and stage, and assessed whether the associations differed for colon cancer (CC) and rectal cancer (RC).

COX-2-selective inhibitors and the risk of upper gastrointestinal bleeding in high-risk patients with previous gastrointestinal diseases: a population-based case–control study

Background : Clinical trials have suggested that cyclo‐oxygenase‐2‐selective inhibitors are associated with a lower risk of upper gastrointestinal bleeding than are non‐selective, non‐aspirin, non‐steroidal anti‐inflammatory drugs. This has not yet been confirmed in studies of patients with an increased susceptibility to upper gastrointestinal bleeding.

Proton pump inhibitor use may not prevent high-grade dysplasia and oesophageal adenocarcinoma in Barrett's oesophagus: A nationwide study of 9883 patients

Proton pump inhibitors (PPI) may potentially modify and decrease the risk for development of oesophageal adenocarcinoma in Barretts oesophagus (BO).