Biomedical subjects

P H Madsen

Publications and source records attributed to P H Madsen.

At least 19 recordsLinked to original sources

PubMed2006

Telomerase activity determined by conventional telomeric repeat amplification protocol and reverse transcriptase-polymerase chain reaction assay in ovarian lesions: a comparison of assays.

OBJECTIVE: Telomerase is capable of restoring telomeric sequence lost during replication. No or low levels of telomerase activity are present in normal somatic cells, whereas up to 85-90% of all cancer cells express telomerase activity, suggesting telomerase as a possible tumor marker. The catalytic subunit, hTERT, correlates with the activity of the enzyme. MATERIAL AND METHODS: Telomerase activity in ovarian tissue was measured by the functional telomeric repeat amplification protocol (TRAP)eze assay, and a quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR) assay measuring the expression of the telomerase catalytic subunit, hTERT. RESULTS: A weakly positive correlation was found between telomerase activity and severity of ovarian disease using the results of the TRAP assay, compared to a strongly positive correlation considering the results obtained in the RT-PCR assay. A statistically significant difference between the benign and borderline groups was present using the RT-PCR assay, allowing for screening for both borderline and primary malignant conditions with a specificity of 97% and a sensitivity of 68%. No significant statistical difference was found between telomerase activity in benign and borderline conditions when using the TRAP assay. When screening for primary malignancy, the specificity and sensitivity rates were 94% and 21%, respectively. CONCLUSIONS: The RT-PCR assay allowed discrimination between benign and borderline and malignant cases, and thereby proved superior to the TRAP assay, which could not discriminate the benign cases from the borderline cases. This suggests that the RT-PCR assay may be useful in screening for both borderline and primary malignancy in ovarian lesions.

Biomarkers, Tumor↗

PubMed2001

Inflammatory activation of neutrophils by Helicobacter pylori; a mechanism insensitive to pertussis toxin.

Chronic active gastritis of the antral mucosa is a characteristic feature of infection with Helicobacter pylori and interactions between bacterial components and inflammatory cells are believed to play an important pathogenic role. Neutrophils stimulated with H. pylori sonicate were demonstrated to release L-selectin (CD62L) expressed on the cellular surface, with a subsequent up-regulation of the beta2-integrins CD11b and CD11c, both in a dose- and time-dependent manner, reaching maximum levels after 45-60 min of stimulation. No changes were observed for the CD11a receptor upon stimulation. The activating properties of H. pylori sonicates on neutrophils were heat-labile and susceptible to protease attack, indicating the protein nature of the activating factor. After size fractionation, the major neutrophil-inducing activity was detected in the high molecular weight fraction exhibiting urease activity. Pertussis toxin was unable to inhibit neutrophil activation by the H. pylori protein(s). We conclude that proteins from H. pylori have a potent inflammatory effect on the surface membrane molecules CD62L, CD11b and CD11c essential for transendothelial migration of neutrophils to areas of inflammation. The neutrophil-activating protein(s) act via a pertussis toxin-insensitive mechanism.

CD18 Antigens↗

PubMed2000

Haemophilic patients with hepatitis C have higher viral load compared to other well-defined patient groups.

Comparison of hepatitis C viral load between different patient populations has been hampered by the use of different technology in individual studies. We had the impression that haemophilic (HAEM) patients had a higher serum load of hepatitis C virus (HCV) compared to other HCV-infected patients. We therefore studied viral load and genotypes in active illicit drug users (IDU), HAEM patients and patients with post-transfusion hepatitis (PTH). The study comprises 225 HCV-RNA positive patients, 117 IDU, 60 HAEM patients and 48 PTH patients. All patients were anti-HIV negative. HCV-RNA was measured with a quantitative reverse transcription polymerase chain reaction (RT-PCR) method, HCV-genotypes were determined with genotype specific primers in RT-PCR in 221 patients. Four patients could not be genotyped with our assay and were excluded. Overall viral load was higher in genotypes 1 and 2 compared to genotype 3, median values of HCV-RNA were 1,400 x 10(3) geq ml(-1), 2,700 x 10(3) geq ml(-1) and 270 x 10(3) geq ml(-1), respectively. HAEM patients had significantly higher viral load for both genotypes 1 and 3 compared to the IDU and PTH patients. In a multiple linear regression model HCV-RNA viral load was independently associated with HAEM and genotype, but not to age, gender or disease duration. In conclusion, HAEM patients have higher viral load than IDU and PTH patients. The reason for this is unknown, but it may be due to host factors or mode of transmission with multiple inoculations.

Adult↗

PubMed1999

Heartburn treatment in primary care: randomised, double blind study for 8 weeks.

OBJECTIVE: To compare the effects and tolerability of omeprazole and cisapride with that of placebo for control of heartburn in primary care patients. DESIGN: Randomised, double blind, placebo controlled study. SETTING: 65 primary care practices in Norway. PARTICIPANTS: 483 untreated patients with complaints of heartburn >/=3 days a week, with at most grade 1 reflux oesophagitis. INTERVENTIONS: Omeprazole 20 mg once daily, cisapride 20 mg twice daily, or placebo for 8 weeks. MAIN OUTCOME MEASURES: Adequate control of heartburn, defined as </=1 day of the past 7 days with no more than mild heartburn, after 4 weeks of treatment. RESULTS: In the all patients treated analysis, adequate control of heartburn was achieved in 71% of patients taking omeprazole, 22% taking cisapride, and 18% taking placebo after 4 weeks of treatment (omeprazole v cisapride and placebo, P<0.0001; cisapride v placebo, non-significant). Results were comparable in patients with or without reflux oesophagitis. In patients treated with omeprazole only, symptom control was achieved significantly more often in patients positive for Helicobacter pylori. Antacid use was 2-3 times greater in patients taking cisapride or placebo than in those taking omeprazole. Relief of non-reflux symptoms did not significantly differ between the three groups. Significantly more patients taking cisapride reported adverse events than those taking omeprazole or placebo. CONCLUSIONS: Omeprazole 20 mg once daily was highly effective in relieving heartburn whereas cisapride 20 mg twice daily was not significantly more effective than placebo.

Anti-Ulcer Agents↗

PubMed1999

Rapid MEN 2A gene carrier identification using primer-specific PCR amplification.

DNA testing is of great importance in families with multiple endocrine neoplasia (MEN) type 2A to identify non-mutant carrying family members and asymptomatic mutation carriers, and also to confirm the diagnosis in patients who already show clinical or biochemical signs of disease. Several point mutations of the RET proto-oncogene on exons 10 and 11 are associated with the disease, which is characterized by medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism. The aim of the present study was to develop and evaluate a simple method, which indicates the mutational status of members of families where the site of the point mutation is known. The method is illustrated by the detection of mutation TGC-->TAC of codon 611, which is one of the well-known mutations associated with MEN 2A. The method involves the PCR technique with allele-specific primers and detection of the amplified sequences with biotinylated probes. There was a clear-cut difference between the readings from affected and unaffected subjects. The subjects had been evaluated independently and all subjects harboring the mutation also had clinical disease. The method provides a simple and reliable diagnostic tool for DNA screening of members of families with a known mutation of the RET-gene.

Biotin↗

PubMed1998

[Brown syndrome in an adult patient with morbus Still].

A 25 year-old woman, known to be suffering from destructive rheumatoid arthritis, was admitted to the hospital due to influenza-like symptoms lasting three weeks. Adult Still's disease was diagnosed. During her disease she developed painful ophthalmoplegia due to tenosynovitis of the superior oblique muscle and tendon sheath (Brown's syndrome). Total resolution was obtained within three weeks of corticosteroid therapy.

Adult↗

PubMed1998

A quantitative HCV-PCR test for routine diagnostics.

The aim of this study was to develop a reliable and simple method for hepatitis C virus (HCV)-PCR using standard, automated laboratory equipment. HCV-RNA was extracted from serum and amplified in a single PCR with an internal standard. The PCR product was detected using fluoroimmunoassay. Quantification was based on external and internal standards. Linearity was observed over a wide range (10-10(7) geq). Mean inter and intra serial coefficients of variation were 35% and 23%, respectively. The limit of quantification was 1000 geq/ml based on intra and inter serial variations, while levels of 110 geq/ml were always detectable. Lower concentrations were intermittently positive. The ability to separate HCV-signals in healthy and infected persons was good, based on the distribution of HCV-signals from 353 random blood donors and 191 patient samples. To illustrate the applicability of the test, HCV-RNA quantification was performed in 11 patients during treatment with interferon alpha-2b. Ten of 11 patients showed a decline in HCV-RNA within the first few weeks of treatment. After four weeks most patients were still HCV-RNA positive but below the limit of quantification. The present method for quantification of HCV-RNA was shown to have sensitivity at the level of nested PCR techniques. Until now HCV-PCR has been complicated, time-consuming and costly, and therefore not suitable for routine diagnostics. The PCR method described here is easy to perform, fast and cost-effective.

Base Sequence↗

PubMed1998

Performance of hepatitis C virus (HCV) antibody test systems in relation to HCV-RNA detection in the diagnosis of HCV infection.

BACKGROUND: Hepatitis C virus antibody (anti-HCV) test systems for screening and confirmation of blood donations have proved their value. The systems were later adopted for diagnosing patients suspected of hepatitis C. OBJECTIVES: 1) to study the clinical value of the recombinant immunoblot assay (RIBA) in routine diagnostics of patients suspected of HCV infection using HCV-PCR as the most definitive test and 2) to compare the performance of RIBA-2 with RIBA-3. MATERIALS: From May 1991 to August 1996 more than 4300 patients were tested for anti-HCV. All anti-HCV (EIA) positive patients were tested with RIBA-2 or RIBA-3 and HCV-PCR. RESULTS: We found no difference in the overall performance of RIBA-2 compared to RIBA-3. There was a tendency to fewer indeterminate results using RIBA-3 compared to RIBA-2 (5% vs. 9%), but this was not statistically significant. The NS5 band in RIBA-3 did not improve sensitivity or predictive value. Of RIBA-2 and RIBA-3 positive patients, 71% and 66% respectively were found to be HCV-RNA positive. Two samples that were negative using RIBA were HCV-RNA positive. CONCLUSION: RIBA testing in anti-HCV (EIA) positive patients added no clinically useful information to the screening results. We have therefore changed the diagnostic strategy so that all anti-HCV (EIA) positive patients are tested for HCV-RNA.

Hepacivirus↗

PubMed1993

The effect of low-dose supplementation with n-3 polyunsaturated fatty acids on some risk markers of coronary heart disease.

Epidemiological data have suggested that a low dose of dietary n-3 polyunsaturated fatty acids from seafood may protect against coronary heart disease. We studied the effect of supplementation with a low dose of very long-chain n-3 fatty acids (0.65 g day-1) on plasma lipids, haemostasis, and neutrophil aggregation. Twenty-four healthy subjects were randomized to supplementation with very long-chain n-3 fatty acids or a control oil for 8 weeks. Laboratory analyses were done twice before and twice at the end of the supplementation period. The supplement with n-3 polyunsaturated fatty acid did not significantly affect plasma lipids or plasma levels of fibrinogen, factor VII, plasminogen activator inhibitor, whole blood aggregation or aggregability of neutrophil leukocytes. Therefore, the potential beneficial effect of very long-chain n-3 fatty acids in coronary heart disease is likely to be mediated through other mechanisms.

Adult↗

PubMed1990

[Fish oil products. Contents of n-3 fatty acids and oxidative break-down products].

Twenty-five fish oil products commercially available in Denmark were examined for their content of n-3 fatty acids. The magnitude of n-3 fatty acid intake was calculated when the dosage recommended by the manufacturers was adhered to. Where the majority of the products were concerned, the intake was much less than the approximately 2 g daily which produces demonstrable effect. Where isolated preparations are concerned, the intake is so limited that this has probably no value. The content of oxidation products in the preparations was also investigated. Compared with the quantity of oxidation products from other sources, the content in the preparations examined is of minor significance.

Fatty Acids↗

PubMed1973