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Biomedical subjects

A Knudsen

Publications and source records attributed to A Knudsen.

At least 19 recordsLinked to original sources

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↗

Yo antibodies in ovarian and breast cancer patients detected by a sensitive immunoprecipitation technique.

Onconeural antibodies are found in patients with cancer and are associated with paraneoplastic neurological syndromes (PNS). The objective of the present study was to assess the frequency of Yo antibodies in ovarian and breast cancer using a sensitive immunoprecipitation technique, and to look for any association of Yo antibodies with neurological symptoms and prognostic factors. A multiwell adapted fluid-phase immunoassay using radiolabelled recombinant cerebellar degeneration related protein (cdr2), produced by coupled in vitro transcription/translation was used for the detection of Yo antibodies. This technique combines high specificity and sensitivity with high sample analysing capacity for the antibody in question. Sera or EDTA-blood from 810 ovarian (n = 557) and breast cancer (n = 253) patients were analysed for Yo antibodies by immunoprecipitation, as well as immunofluorescence and immune blots. Two hundred healthy blood donors and sera from 17 patients with paraneoplastic cerebellar degeneration and Yo antibodies served as controls. Immunoprecipitation was more sensitive in detecting Yo antibodies than immunofluorescence and immune blots. The prevalence of Yo antibodies was 13/557 (2.3%) in ovarian cancer and 4/253 (1.6%) in breast cancer using immunoprecipitation. Yo antibodies were not correlated with specific histological subgroups. The Yo index of ovarian cancer patients in FIGO stage IV was higher compared to FIGO stage I-III. The prevalence of Yo antibodies was 3 times higher in patients with stage III breast cancer than in stage I and II. Only 2/17 (11.8%) patients with Yo antibodies detected during the screen of 810 cancer patients had PNS. The results show that the prevalence of Yo antibodies is low in ovarian and breast cancer. Yo antibodies may be associated with advanced cancer, but less often with PNS.

Adenocarcinoma↗

cDNA expression library screening for identification of novel onconeural antigens.

Paraneoplastic neurological disorders occur as a remote effect of cancer. Tumor cells expressing neuron-specific proteins elicit an autoimmune response, resulting in the production of various antibodies. The antibodies are usually associated with different syndromes, but the identity of many of the antigens is still unknown. Screening a cDNA expression library is a powerful technique that allows identification of previously uncharacterized antigens. By using patient sera containing antibodies, the antigens of interest can be isolated and further characterized.

Antibodies, Neoplasm↗

Endothelial cell adhesion molecules in healthy adults during acute hyperhomocysteinemia and mild hypertriglyceridemia.

OBJECTIVE: Hyperhomocysteinemia and hypertriglyceridemia are independently associated with atherosclerotic disease. The process of atherogenesis involves inflammation and endothelial dysfunction. We tested whether concurrent acute hyperhomocysteinemia and mild hypertriglyceridemia increase the concentrations of circulatory cellular adhesion molecules in healthy subjects. STUDY DESIGN AND METHODS: Twelve healthy volunteers aged 37.5 years (range, 25-51) participated in the present study. The concentrations of plasma total homocysteine (p-tHcy), serum triglycerides, circulatory cellular adhesion molecules (CAMs), and concentrations of nitrate were measured at 0 (fasting), 2, 4, and 6 h after loading with (1) methionine, (2) fat, (3) methionine + fat, and (4) water (control). Wash out period between each loading was >or=1 week. RESULTS: Percent relative changes from baseline in the concentrations of p-tHcy, 2, 4, and 6 h after methionine and methionine + fat were significantly different from after water and fat loading. Changes in the concentrations of serum triglycerides 2 h after fat loading were significantly different from water loading, whereas methionine + fat loading caused a significant difference after 2, 4, and 6 h. We detected a synergistic increase in the triglyceride area response to methionine + fat loading. We detected also a significant difference in percent relative changes in the concentrations of P-selectin (PSEL) (P = 0.02), E-selectin (ESEL) (P = 0.003), and vascular cell adhesion molecule-1 (VCAM-1) (P = 0.005) 6 h after methionine + fat loading as compared to water loading. There was an additive increase in the PSEL area response to methionine + fat loading. Furthermore, area response to VCAM was greater to methionine loading than water loading (P = 0.01). A decrease in the concentration of NO(3) was more pronounced after methionine + fat loading and a significantly decreased area response of nitrate to methionine + fat loading was detected than to area response to water loading (P = 0.002). CONCLUSION: Inflammatory activation of the endothelium takes place during concurrent transient hyperhomocysteinemia and mild hypertriglyceridemia.

Acute Disease↗

Tobacco--enemy of public health from conception to grave.

UNLABELLED: Parental smoking and the pregnant mother or infant exposure to environmental tobacco smoke (ETS) is connected with extraordinarily adverse health consequences for the foetus and child. This morbidity and even mortality is preventable. CONCLUSION: From the perspective of the foetus and the child, every measure should be taken to promote smoking cessation by their parents and prevent exposure to ETS.

Breast Feeding↗

Characteristics and prognostic impact of plasma fibrin monomer (soluble fibrin) in patients with coronary artery disease.

We measured fibrin monomer (FM), soluble fibrin, as a marker of thrombin activity in plasma samples obtained in parallel with the first two routine samples for cardiac markers in 165 patients with acute chest pain admitted consecutively to our hospital. A reference limit of FM in a healthy population was set at 3.0 mg/l. Elevated plasma FM was observed in 48.8% of patients with acute coronary syndromes, in 42.3% of patients with specific non-coronary disease, in 31.5% of those with stable angina pectoris and in 18.2% of patients with non-specific chest pain. No significant difference was observed between sample 1 and sample 2 in patients not receiving thrombolytic treatment during the sampling period (P = 0.46). In patients with coronary artery disease, FM was significantly related to the level of cardiac troponin T (P = 0.001), but no correlation was observed between the individual plasma FM and cardiac troponin T values. Outcome analysis during the following 30 months after the index event in patients with acute coronary syndromes revealed higher FM levels in those with coronary re-events or death than in patients without new events (P = 0.001). This observation indicates a prognostic potential of FM in risk evaluation of patients with coronary artery disease.

Adult↗

Telomerase activity, MIB-1, PCNA, HPV 16 and p53 as diagnostic markers for cervical intraepithelial neoplasia.

The present investigation evaluated the relationship between dysplasia of the uterine cervix and telomerase activity, expression of p53, MIB-1 and PCNA. Telomerase activity was measured on cervical cytobrush material from 126 women suspected of having dysplasia and 61 controls using the telomeric repeat amplification protocol. Immunohistochemistry was used to detect the tumor suppressor protein p53 and cell proliferation, the latter by MIB-1 and PCNA expression. Infection with human papillomavirus 16 was detected by PCR amplification and Southern blot hybridization of DNA extracted from the same brush material. Positive telomerase activity was found in 5 of 43 (11.6%) normal samples, 12 of 57 (21.1%) samples with inflammation or koilocytosis, 7 of 17 (41.2%) CIN 1 (cervical intraepithelial neoplasia, grade 1), 8 of 20 (40.0%) CIN 2, and 25 of 42 (59.5%) CIN 3/ CIS. Telomerase activity was significantly related to the level of dysplasia (p<0.001) and proliferation measured by MIB-1 (p=0.019), but not to the level of PCNA (p=0.445), HPV 16 status (p=0.098) or staining for p53 (p=0.271). Dysplasia was also related to PCNA, MIB1, p53, and presence of HPV 16. A sequential increase in the examined parameters, paralleling the progression of abnormality, was observed. PCNA and telomerase showed an increase in CIN 1, MIB-1 and HPV16 in CIN 2, and finally p53 in CIN 3/CIS.

Adolescent↗

General practitioners' reactions to non-compliant patients.

OBJECTIVE: To examine how general practitioners (GPs) respond to patients who are non-compliant with medical advice and who doctors believe act irresponsibly towards their health. DESIGN: Quantitative analysis of responses to questionnaire with case histories. SETTING AND SUBJECTS: 93 questionnaires completed by a random stratified sample of Norwegian GPs. MAIN OUTCOME MEASURES: Scores relating to GPs' feelings and choice of main and sub-strategies for further treatment of patients. RESULTS: The respondents typically felt discouraged or unaffected by non-compliant patients, younger doctors more often felt helpless while older ones were more content, and female doctors more often than male doctors felt irritated or angry. The main strategy preferred was to give the patient a new appointment. The young, the inexperienced, and females tended more often to ask a colleague for advice or refer to a specialist. Patient-centred sub-strategies were generally preferred, especially by younger doctors. CONCLUSION: GPs' feelings towards and strategies for dealing with non-compliant patients vary, and the doctor's age, sex and clinical experience are central variables.

Adult↗

Impact of smoking on the duration of breastfeeding in mothers with insulin-dependent diabetes mellitus.

UNLABELLED: The effect of smoking on breastfeeding was studied in 252 mothers with insulin-dependent diabetes mellitus (IDDM) giving birth in the period 1985-1995 and of whom 31% were classified as White group B, 16% group C, 37% group D and 16% group F or R. As part of a centralized regimen a detailed smoking history was taken during pregnancy. Forty-six percent were smokers. In 1997, a questionnaire was sent out asking for information on the duration of breastfeeding. The response rate was 87%. The duration of breastfeeding was significantly longer in the non-smoking group (p = 0.004). Fifty-five percent of non-smokers versus 33% of smokers were still breastfeeding 4 mo after birth. A strong dose-response relationship was established (p = 0.009). Cox multiple regression analysis showed a significantly negative influence of smoking (p = 0.01) and of hospitalization of the infants during the first year of life (p = 0.02) and a significantly positive influence of maternal age (p = 0.02) and birthweight (p = 0.03) on the length of breastfeeding. The breastfeeding curves for non-smokers and smokers were mainly divergent in the first month after birth, suggesting that the effect of smoking on breastfeeding is mainly exerted during that period. CONCLUSION: Smoking exerted a strong, negative, dose-dependent influence on breastfeeding duration in mothers with IDDM. Given the hazards of smoking, the advantages of breastfeeding and the possible link between being breastfed and later development of diabetes mellitus, these results should be taken into consideration when counselling pregnant women with IDDM about smoking.

Adult↗

Pain-relieving effect of sucrose in newborns during heel prick.

We assessed the effect of sucrose as a pain reliever in a population of newborns when cuddled and comforted during heel prick for diagnosis of phenylketonuria. In addition, the influences of gender, gestational age, postnatal age, ponderal index and behavioural state of the infant before the heel prick were studied, as judged by the neonatal infant pain scale (NIPS) score, on crying time (CT) and subsequent NIPS score. 100 healthy full-term infants were enrolled in this double-blind, randomized controlled trial. Before the heel prick, the newborns, when cuddled by the parent(s), were either given 2 ml 50% sucrose solution or 2 ml sterile water. The sessions were videotaped and analyzed for determination of CT and NIPS scores. The frequency distribution of CT showed a bimodal pattern in both the sucrose and the placebo groups. Sucrose significantly reduced CT and NIPS scores after the heel prick. No influence of gender, gestational age, postnatal age or ponderal index on CT was found. NIPS scores before the heel prick correlated significantly and positively with CT and subsequent NIPS scores in both the sucrose and the placebo groups. Intra-orally administered sucrose given before heel prick can be recommended as a useful pain reliever. Furthermore, the findings indicate that factors calming the newborn and creating low NIPS scores before the procedure can reduce the pain reaction equivalently and additively to sucrose administration.

Aging↗

Cephalocaudal progression of jaundice in newborns admitted to neonatal intensive care units.

The influence of several clinical factors on the cephalocaudal progression of neonatal jaundice was investigated in 377 newborns admitted to the neonatal intensive care unit for various reasons. Multiple regression analysis showed that, beyond the relationship to the plasma bilirubin concentration, the cephalocaudal color gradient was significantly, negatively related to gestational and postnatal age. Furthermore, the cephalocaudal progression of jaundice seemed more extended in females compared to males. The results are in agreement with a theory explaining that the cephalocaudal color gradient is due to conformational changes in the newly formed bilirubin albumin complexes.

Age Factors↗

[Headache, fatigue and edema of the lower limbs during the third trimester of normal pregnancy].

A series of 180 pregnant women with normal pregnancies participated in the study. A questionnaire concerning the presence of headache, fatigue and oedema of the lower limbs was filled out daily from the 30th gestational week to delivery. After the study period 120 questionnaires, of whom eight were excluded, were available for analysis. The weekly prevalences of headache and fatigue during the observation-period were nearly constant with values of 20% and 50%, respectively. The weekly prevalence of oedema increased significantly from 20% in the 31st week to 60% in the 42nd gestational week. Thirty-five percent had not suffered from headache, 22% did not report fatigue, and 42% did not describe oedema at all during the third trimester. The prevalence of headache and fatigue correlated significantly to increasing parity whereas headache was significantly correlated to decreasing age. Headache, fatigue, and oedema are common symptoms in the third trimester of normal pregnancy, and as such their presence alone should not usually give cause for suspicion of disease.

Edema↗

Prediction and non-invasive assessment of neonatal jaundice in the term healthy newborn infant.

The maternal and umbilical cord bilirubin concentration at delivery, a yellow skin colour on the first postnatal day, an increase in the yellow skin colour during the first 24 h or postnatal life, and carbon monoxide excretion are all associated with the later development of neonatal jaundice in the healthy, mature newborn infant. Based on the results from these methods, and especially when the results from two or more of the methods are combined, it is possible to define low- and high-risk groups as far as subsequent jaundice is concerned. If jaundice develops, yellow skin colour measurements can often replace plasma bilirubin determinations. Dependent upon the local current consensus for bilirubin determinations, around 50% of plasma bilirubin determinations can be avoided. Recent research suggests that yellow skin colour measurements may provide information concerning the risk of bilirubin encephalopathy, in addition to their relation to the plasma bilirubin concentration.

Bilirubin↗

Transcutaneous bilirubinometry in neonatal intensive care units.

AIMS: To study the influence of several clinical and paraclinical factors on the association between jaundice meter readings and plasma bilirubin concentration; and to comment on the usefulness of the jaundice meter as a screening device for hyperbilirubinaemia in neonatal intensive care units. METHODS: Three hundred and seventy seven newborn babies admitted to the neonatal intensive care unit for various causes were included in the study. When the plasma bilirubin concentration needed to be determined for clinical reasons, the extent of the yellow skin colour was measured transcutaneously, using a jaundice meter. The haemoglobin concentration was also determined. This had no independent influence on the jaundice meter readings. The yellow skin colour was significantly and positively correlated with the bilirubin concentration and the presence of respiratory distress syndrome (RDS), and negatively with gestational age and postnatal ages. CONCLUSIONS: These findings were interpreted as being due to variations in the ability of albumin to bind bilirubin, and in the basal yellow skin colour. It was impossible to derive simple criteria for detection of hyperbilirubinemia by jaundice meter readings in this study group.

Bilirubin↗

[Transcutaneous evaluation of icterus in healthy mature newborn infants. A substitution for blood tests].

The conventional determination of plasma bilirubin concentration in the icteric mature healthy newborn infants may frequently be replaced by transcutaneous assessment. Depending on the desired exactitude and the prevailing consensus on plasma bilirubin determination it is possible to halve the necessary number of blood tests. However, the yellow colour of the skin is influenced by several factors. Thus, transcutaneous measurements of the plasma bilirubin concentration are inaccurate. The yellow colour of the skin should be considered as an important parameter which, at least theoretically, provides information concerning the risk of bilirubinencephalopathy beyond the mere relationship to the plasma bilirubin concentration. Introduction of the method as a test of hyperbilirubinaemia requires taking a stand on several practical circumstances, determination of a standard curve with the risk of selection borne in mind and the establishment of cut-off levels.

Humans↗

Upper gastrointestinal symptoms in the third trimester of the normal pregnancy.

OBJECTIVES: To report on the prevalence of well-being, heartburn, nausea, and vomiting related to gestational week, parity, and age in the third trimester of the normal pregnancy. STUDY DESIGN: Self-administered questionnaire filled in daily by 180 women from 31st gestational week to delivery. RESULTS: The study was completed by 120 women. The weekly prevalence of well-being decreased from 50% at the 31st gestational week to 24% at the 42nd gestational week (P = 0.00001). The weekly prevalence of heart-burn (approximately 60%), nausea (approximately 16%) and vomiting (approximately 7%) was nearly constant throughout the study period. Well-being was inversely related to parity, (P = 0.006), heartburn positively related to age (P = 0.016), and nausea and vomiting inversely related to age (P = 0.003 and P = 0.044). CONCLUSION: Discomforts are customary in the third trimester of normal pregnancy. However, heartburn and especially nausea and vomiting appeared occasionally and were not present for longer periods. The findings that heartburn, nausea and vomiting had different relations to age may suggest different etiologies.

Adult↗