Search PubMed⌕ Search

Biomedical subjects

L R Nielsen

Publications and source records attributed to L R Nielsen.

15 recordsLinked to original sources
PubMed2006

Simulation model estimates of test accuracy and predictive values for the Danish Salmonella surveillance program in dairy herds.

The Danish government and cattle industry instituted a Salmonella surveillance program in October 2002 to help reduce Salmonella enterica subsp. enterica serotype Dublin (S. Dublin) infections. All dairy herds are tested by measuring antibodies in bulk tank milk at 3-month intervals. The program is based on a well-established ELISA, but the overall test program accuracy and misclassification was not previously investigated. We developed a model to simulate repeated bulk tank milk antibody measurements for dairy herds conditional on true infection status. The distributions of bulk tank milk antibody measurements for infected and noninfected herds were determined from field study data. Herd infection was defined as having either >or=1 Salmonella culture-positive fecal sample or >or=5% within-herd prevalence based on antibody measurements in serum or milk from individual animals. No distinction was made between Dublin and other Salmonella serotypes which cross-react in the ELISA. The simulation model was used to estimate the accuracy of herd classification for true herd-level prevalence values ranging from 0.02 to 0.5. Test program sensitivity was 0.95 across the range of prevalence values evaluated. Specificity was inversely related to prevalence and ranged from 0.83 to 0.98. For a true herd-level infection prevalence of 15%, the estimate for specificity (Sp) was 0.96. Also at the 15% herd-level prevalence, approximately 99% of herds classified as negative in the program would be truly noninfected and 80% of herds classified as positive would be infected. The predictive values were consistent with the primary goal of the surveillance program which was to have confidence that herds classified negative would be free of Salmonella infection.

Animals↗
PubMed2006

Use of IgG avidity ELISA to differentiate acute from persistent infection with Salmonella Dublin in cattle.

AIMS: To investigate whether an immunoglobulin (Ig)G avidity ELISA can be used to differentiate between acute and persistent infection with Salmonella (S.) Dublin in cattle. To determine whether the IgG isotype, IgG(1) and IgG(2) responses in acute and persistent infections differ. METHODS AND RESULTS: Animals were selected from two herds with long-term infection (years) and two herds recently infected (<3 months). Forty-seven animals were categorized into groups based on the persistence of their antibody level in milk. Based on titre from two serial dilutions the avidity index (AI) was calculated for IgG (IgG-AI), IgG(1) (IgG(1)-AI) and IgG(2) (IgG(2)-AI). The mean IgG-AI for suspected carrier animals with either persistently high (group 1) or persistently high to medium high (group 2) antibody levels was significantly (P = 0.003) higher (32.1% and 38.4%) than for acutely infected animals (21.7% and 22.3%). The probability of being a suspect carrier was associated with IgG-AI, antibody level in the sample and age. However, the effect of age could be the result of a biased sample selection. Specificities and sensitivities were calculated at a range of cut-off values for IgG-AI and IgG(1)-AI. Overall, IgG(2)-AI was high compared with IgG(1)-AI, and there was no difference in IgG(2)-AI between infection groups. There was no difference in the ratio IgG(2):IgG(1) for acute and persistent infection groups. CONCLUSIONS: Assuming that a persistently high antibody response is indicative of persistent infection with S. Dublin in cattle, it can be concluded that the IgG-AI can aid in differentiating between acute and long-term infection on herd level. However, for the test to be useful as an alternative tool to repeated sampling over time for detection of persistently infected carriers during control strategies in cattle herds, the test needs to be optimized and studied further in a larger sample of well-characterized infections in cattle. The affinity of IgG(2) is higher than IgG(1) early in the S. Dublin infection. There appears to be no difference in the IgG(2)-AI between the acute and chronic infection stages. SIGNIFICANCE AND IMPACT OF THE STUDY: For decades the strategies for detection of persistently infected cattle in S. Dublin infected herds have involved repeated bacteriological culture of faecal samples or repeated antibody measurements over several months. Both methods are time consuming and costly, leaving a new method for detection of carrier animals based on a single sampling highly desirable. This study illustrates a tool, IgG-AI, which may prove useful, although more validation of the method is required before it is used in practice.

Acute Disease↗
PubMed2006

Reduced prevalence of early preterm delivery in women with Type 1 diabetes and microalbuminuria--possible effect of early antihypertensive treatment during pregnancy.

AIMS: In normotensive women with Type 1 diabetes and microalbuminuria we previously found preterm delivery (< 34 weeks) in 23% of the pregnancies. Antihypertensive treatment was initiated in late pregnancy when preeclampsia was diagnosed and diastolic blood pressure > 90 mmHg. From April 2000 our routine was changed and early antihypertensive treatment with methyldopa was initiated if antihypertensive treatment was given prior to pregnancy, if urinary albumin excretion (UAE) was > 2 g/24 h, or blood pressure > 140/90 mmHg. The present study describes the impact of this more aggressive antiypertensive treatment in the prevalence of preterm delivery. METHODS: The old cohort (1995-1999) consisted of 26 and the new cohort (2000-2003) of 20 pregnant women with Type 1 diabetes and microalbuminuria. All were referred before gestational week 17. RESULTS: The cohorts were comparable with regard to age, diabetes duration, prepregnancy body mass index, HbA1c, blood pressure 121 (13)/71 (8) vs. 121 (14)/73 (8) mmHg [mean (sd)] and early UAE 69 (16-278) vs. 74 (30-287) mg/24 h (geometric mean and range). Antihypertensive treatment was initiated in the old cohort at 29 (20-33) weeks, n = 9, and in the new at 13 (0-34) weeks, n = 10. The prevalence of preterm delivery before 34 weeks was reduced from 23% to zero (P = 0.02), preterm delivery before 37 weeks from 62% to 40% (P = 0.15) and preeclampsia from 42% to 20% (P = 0.11). Perinatal mortality occurred in 4% vs. 0%. Birth weight was 3124 (767) g vs. 3279 (663) g. CONCLUSION: Introduction of early antihypertensive treatment with methyldopa in normotensive pregnant women with Type 1 diabetes and microalbuminuria resulted in a significant reduction in preterm delivery before gestational week 34.

Adult↗
PubMed2004

Salmonella Dublin infection in dairy cattle: risk factors for becoming a carrier.

Long-term Salmonella Dublin carrier animals harbor the pathogen in lymph nodes and internal organs and can periodically shed bacteria through feces or milk, and contribute to transmission of the pathogen within infected herds. Thus, it is of great interest to reduce the number of new carrier animals in cattle herds. An observational field study was performed to evaluate factors affecting the risk that dairy cattle become carrier animals after infection with Salmonella Dublin. Based on repeated sampling, cattle in 12 Danish dairy herds were categorized according to course of infection, as either carriers (n = 157) or transiently infected (n = 87). The infection date for each animal was estimated from fecal excretion and antibody responses. The relationship between the course of infection (carrier versus transiently infected) and risk factors were analyzed using a random effect multilevel, multivariable logistic regression model. The animals with the highest risk of becoming carriers were heifers infected between the age of 1 year and 1st calving, and cows infected around the time of calving. The risk was higher in the first two quarters of the year (late Winter to Spring), and when the prevalence of potential shedders in the herd was low. The risk also varied between herds. The herds with the highest risk of carrier development were herds with clinical disease outbreaks during the study period. These findings are useful for future control strategies against Salmonella Dublin, because they show the importance of optimized calving management and management of heifers, and because they show that even when the herd prevalence is low, carriers are still being produced. The results raise new questions about the development of the carrier state in cattle after infection with low doses of Salmonella Dublin.

Animals↗
PubMed2004

Molecular differentiation within and among island populations of the endemic plant Scalesia affinis (Asteraceae) from the Galápagos Islands.

Molecular variance was estimated in seven populations of the endemic species Scalesia affinis within and among islands of the Galapagos. The analysis, based on 157 polymorphic AFLP markers, revealed a high differentiation among populations, of which most was partitioned among islands. In addition, the information content of AFLP markers was tested with sets of discriminant analyses based on different numbers of AFLP markers. This indicated that the markers were highly informative in discriminating the populations. Although one of four populations from the island Isabela was sampled from a volcano 100 km away from the remaining populations, this population resembled the others on Isabela. The partitioning of molecular variance (AFLP) resulted in two unities, one consisting of populations from Isabela and one of populations from Santa Cruz and Floreana. The differentiation in two chloroplast microsatellites was higher than for AFLP markers and equally partitioned among populations within islands as among islands. Thus, gene flow via fruits within islands is as limited as among islands. The lower differentiation within islands in the nuclear AFLP markers may thus indicate that gene flow within islands is mostly accounted for by pollen transfer. S. affinis is the only species in the genus that is not listed in 2000 IUCN Red List of Threatened Species. However, due to prominent grazing and land exploitation, some populations have recently been reduced markedly, which was reflected in lower diversity. As inbreeding depression is present in the species, the rapid bottlenecks are threats to the populations.

Asteraceae↗
PubMed2004

Evaluation of an indirect serum ELISA and a bacteriological faecal culture test for diagnosis of Salmonella serotype Dublin in cattle using latent class models.

AIMS: To evaluate a conventional bacteriological test based on faecal culture and an indirect serum ELISA for detection of S. Dublin infected cattle. To compare the predictive values of the two tests in relation to the prevalence. METHODS AND RESULTS: A total of 4531 paired samples from cattle in 29 dairy herds were analysed for presence of S. Dublin bacteria in faeces and immunoglobulins directed against S. Dublin lipopolysaccharide in an indirect serum ELISA. Sensitivity and specificity were estimated at two ELISA cut-off values using a validation method based on latent class models, which presumably provides less biased results than traditional validation methods. Stratification of data into three age groups gave significantly better estimates of test performance of the ELISA. Receiver operating characteristic (ROC) curves were constructed for comparison of overall performance of the ELISA between the three age groups. The sensitivity of the faecal culture test was low (6-14%). ELISA appeared to have a higher validity for animals aged 100-299 days of age than older or younger animals. Overall, the negative predictive value of the ELISA was 2-10 times higher than for the faecal culture test at realistic prevalence of infection in the test population. CONCLUSIONS: The diagnostic sensitivity of the faecal culture test for detection of S. Dublin is poor, the specificity is 1. The superior sensitivity and negative predictive value of the serum ELISA makes this test preferable to faecal culture as an initial screening test and for certification of herds not infected with S. Dublin. SIGNIFICANCE AND IMPACT OF THE STUDY: A quantitative estimate of the sensitivity of a faecal culture test for S. Dublin in a general population was provided. ELISA was shown to be an appropriate alternative diagnostic test. Preferably, samples from animals aged 100-299 days of age should be used as these give the best overall performance of the ELISA. Plots of ROC curves and predictive values in relation to prevalence facilitates optimisation of the ELISA cut-off value.

Animals↗
PubMed1998

K-ras mutations in sinonasal adenocarcinomas in patients occupationally exposed to wood or leather dust.

Of 39 males diagnosed with sinonasal adenocarcinomas over 30 years in the Lund University Hospital catchment area (1.5 million inhabitants), archival tumor tissue was available from 29. Of these, 16 had been exposed to wood dust and three had been exposed to leather dust. The intestinal-type and papillary adenocarcinomas were more common in the exposed patients (P = 0.0002, Fisher's exact test). The tumors from all but one of the 29 sinonasal adenocarcinomas could be analyzed for point mutations at codons 12, 13 and 61 of the K-ras gene. Four mutations were detected in the 28 tumors. The three mutations in the patients exposed to wood and leather dust were all G:C --> A:T transitions, with two at position 2 of codon 12 and one at position 2 of codon 13. The high proportion of G:C --> A:T mutations in this rare tumor may reflect a genotoxic agent in wood and leather dust.

Adenocarcinoma↗
PubMed1996

Somatic mutation detection in human biomonitoring.

Somatic cell gene mutation arising in vivo may be considered to be a biomarker for genotoxicity. Assays detecting mutations of the haemoglobin and glycophorin A genes in red blood cells and of the hypoxanthine-guanine phosphoribosyltransferase and human leucocyte antigenes in T-lymphocytes are available in humans. This MiniReview describes these assays and their application to studies of individuals exposed to genotoxic agents. Moreover, with the implementation of techniques of molecular biology mutation spectra can now be defined in addition to the quantitation of in vivo mutant frequencies. We describe current screening methods for unknown mutations, including the denaturing gradient gel electrophoresis, single strand conformation polymorphism analysis, heteroduplex analysis, chemical modification techniques and enzymatic cleavage methods. The advantage of mutation detection as a biomarker is that it integrates exposure and sensitivity in one measurement. With the analysis of mutation spectra it may thus be possible to identify the causative genotoxic agent.

Environmental Monitoring↗
PubMed1995

Detection of ten new mutations by screening the gene encoding factor IX of Danish hemophilia B patients.

Hemophilia B is caused by a wide range of mutations. In order to characterize the mutations among patients in Denmark, we have systematically screened the entire coding region, the promoter region and exon flanking sequences of the gene encoding factor IX using single strand conformation and heteroduplex analyses. Patients from 32 different families were examined, and point mutations (23 different) were found in all of them. Ten of the mutations have not been reported by others; they include a splice site mutation, a single base pair deletion, and missense mutations. Notably, the study contains a female patient and a previously described Leyden mutation. In ten families with sporadic cases of hemophilia B, all 10 mothers were found to be carriers. The origin of two of these mutations was established.

Base Sequence↗
PubMed1989

Analysis of the decreased NK (natural killer) activity in lung cancer patients, using whole blood versus separated mononuclear cells.

The aim of this study was to analyze whether a whole blood assay would give a more correct measure of NK activity than assays using separated mononuclear cells (SMNC). We found that the NK activity of whole blood was higher than the NK activity of SMNC in the 28 lung cancer patients investigated (p = 0.01), whereas this difference between the assays could not be demonstrated in the 29 healthy controls. Since no differences were found between the NK activity of washed blood, SMNC, and monocyte-depleted lymphoid cells, there was no indication that the lower NK activity of SMNC in comparison with whole blood was due to cell loss or to a systematic disturbing effect due to monocytes. The possible effect of plasma factors on the whole blood NK activity was analyzed by comparing whole blood and washed blood. The NK activity of whole blood was increased in comparison with washed blood in the lung cancer patients (p less than 0.0001) indicating a stimulatory effect of plasma. Further, the finding that the reactive capability of lymphocytes from cancer patients was higher than in controls could indicate preactivation of the lymphocytes from the cancer patients due to the presence of stimulatory plasma factors. The NK activity of lung cancer patients was lower than the NK activity of healthy controls. The difference was found to be smaller with whole blood than with SMNC as effector cells, although both differences were significant. The decreased NK activity of cancer patients could be due to blocking immune complexes (IC), but we found no evidence for circulating or cell-bound IC in the lung cancer patients.

Adult↗
PubMed1988

A polyclonal IgM-RF enzyme-linked immunosorbent assay for the detection of circulating immune complexes.

A microplate-adapted polyclonal IgM-rheumatoid factor enzyme-linked immunosorbent assay (pIgM-RF ELISA) for the detection of circulating immune complexes (cIC) is presented. The assay involves the competitive binding of cIC and horseradish peroxidase conjugated aggregated human IgG (HRP-AHG) to solid-phase bound polyclonal IgM-RF (pIgM-RF). Aggregated human IgG (AHG) inhibited the binding of HRP-AHG to pIgM-RF in a dose-dependent way. The detection limit of the assay was about 125 ng AHG/ml diluted serum. The coefficients of variation for the assay varied from 5.0 to 14.7% for intra-assay runs and from 4.5 to 13.8% for inter-assay runs. The levels of cIC in sera from 29 patients with systemic lupus erythematosus (SLE), 85 untreated patients with breast cancer and 105 blood bank donors were studied by the pIgM-RF ELISA. Increased levels of cIC were demonstrated in 41.4% of the SLE group, in 8.2% of the breast cancer group, and in 1.9% of the normal control group. The difference in cIC activity between the SLE group and the normal control group was statistically significant.

Adult↗
PubMedDate not supplied

Lymphocyte glutathione peroxidase activity during exacerbations in multiple sclerosis.

Glutathione peroxidase, one of the major antioxidants in the human brain, has been found to have decreased activity in patients suffering from multiple sclerosis (MS). This study compares the activity of lymphocyte glutathione peroxidase (L-GSH-px) in MS patients suffering from acute relapses with clinically stable MS patients and with control patients referred with nondemyelinating neurological diseases. All three groups showed an increase of mean enzymatic activity (MEA) during the observation period. The highest MEA in this study was observed in the MS groups. However, there were no significant differences in the L-GSH-px activity in the three groups. These results are not in accordance with previous investigations, and the need for further research in this field is emphasized.

Adult↗
PubMedDate not supplied

Detection of the plasma cholinesterase K variant by PCR using an amplification-created restriction site.

Ten individuals registered at the Danish Cholinesterase Research Unit were examined at the DNA level for the presence of the K allele of plasma cholinesterase, using amplification-created restriction sites (ACRSs). A further nine members of a family registered at the unit were tested for mutations of the K and atypical variants. The frequency of the K allele was calculated from examination of normal material from 25 individuals, representing 50 random alleles. The results show that the ACRS method successfully demonstrates the presence of the K variant, whose frequency in the Danish population was found to be 0.18. We conclude that this technique is a reliable and rapid non-radioactive diagnostic assay for detecting the plasma cholinesterase K variant.

Alleles↗