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Biomedical subjects

K Hagen

Publications and source records attributed to K Hagen.

At least 37 records · Page 2Linked to original sources
PubMed2002

Blood pressure and risk of headache: a prospective study of 22 685 adults in Norway.

OBJECTIVES: Prevalence studies of the association between blood pressure and headache have shown conflicting results. The aim was to analyse the relation between blood pressure and risk of headache in a prospective study. METHODS: A total of 22 685 adults not likely to have headache, had their baseline blood pressure measured in 1984-6, and responded to a headache questionnaire at follow up 11 years later (1995-7). The relative risk of headache (migraine or non-migrainous headache) was estimated in relation to blood pressure at baseline. RESULTS: Those with a systolic blood pressure of 150 mm Hg or higher had 30% lower risk (risk ratio (RR)=0.7, 95% CI 0.6-0.8) of having non-migrainous headache at follow up compared with those with systolic pressure lower than 140 mm Hg. For diastolic blood pressure, the risk of non-migrainous headache decreased with increasing values, and these findings were similar for both sexes, and were not influenced by use of antihypertensive medication. For migraine, there was no clear association with blood pressure. CONCLUSION: In the first prospective study of blood pressure and the risk of headache, high systolic and diastolic pressures were associated with reduced risk of non-migrainous headache. One possible explanation may be the phenomenon of hypertension associated hypalgesia, which probably involves the baroreflex system influencing nociception in the brain stem or spinal cord.

Adult↗
PubMed2001

Physiotherapy interventions for ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic rheumatic disease. Due to the consequences of the disease, physiotherapy is regarded to be an important part of the treatment. OBJECTIVES: The objective is to summarise the available scientific evidence on the effectiveness of physiotherapy interventions in the management of AS. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group Trial register, Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL and Pedro up to February 2000 for all relevant publications, limited to English and Scandinavian languages. The reference lists of relevant articles were checked and the authors of included articles were contacted. SELECTION CRITERIA: We included randomised and quasi randomised studies where the participants were patients with AS, classified by the New York criteria, and where at least one of the comparison groups received some kind of physiotherapy. The main outcomes of interest were spinal mobility, pain, stiffness, physical function and global assessment of change. DATA COLLECTION AND ANALYSIS: Both reviewers independently selected trials for inclusion, extracted data and assessed trial quality. Investigators were contacted to obtain missing information. MAIN RESULTS: Three trials were included with 241 participants, and all were assessed to have moderate to high risk of bias. Two trials compared the effect of supervised group physical therapy with an individualised home exercise program, and reported differences in favour of the supervised group. For pain and stiffness, the relative difference in change from baseline for the supervised group compared to the home exercise group was 50% after treatment. One trial compared an individual program of exercises and disease education with no intervention, and found differences in favour of the exercise group. REVIEWER'S CONCLUSIONS: The tendency toward positive effects of physiotherapy, in the management of AS, call for further research in this field in order to reach sufficient evidence on which physiotherapy modalities and applications are to be recommended. New trials should address other physiotherapy interventions commonly used in practice. There is not sufficient evidence yet available to base recommendations for or against the use of physiotherapy interventions for ankylosing spondylitis.

Ambulatory Care↗
PubMed2001

Chronic idiopathic anal pain: analysis of ultrasonography, pathology, and treatment.

PURPOSE: This study was undertaken to analyze whether intra-anal ultrasound examination, anorectal physiologic evaluation, and histopathologic examination in patients with chronic idiopathic anal pain presented any common features and whether the results of different treatment modalities correlated with these findings. METHODS: Eighteen patients who met the criteria for chronic idiopathic anal pain were studied. All had an intra-anal ultrasound examination and a complete anorectal physiologic evaluation. In a selected group of patients, ultrasound-guided biopsy samples were taken from pathological areas in the internal and external sphincter. Treatment consisted of analgesics only in four patients, 0.2 percent nitroglycerin ointment in four, and ultrasound injection of botulin (botulinum toxin, Botox) into the intersphincteric space in nine. Two patients, including one who was previously treated with botulin, ultimately had a colostomy. RESULTS: Four patients were managed satisfactorily on analgesic treatment under the guidance of the hospital's pain clinic. Nitroglycerin ointment resulted in temporary pain relief in one of four patients. Injection of botulin resulted in a permanent improvement in four patients, a temporary improvement in one patient, and no effect in four patients. Two patients had a colostomy, resulting in complete pain relief. The effect or lack of effect of nitroglycerin ointment and botulin was not related to changes in anal pressure. CONCLUSION: Chronic idiopathic anal pain is a condition of unknown origin for which no proven therapy exists. As in other syndromes based on muscular dystonia, some patients may benefit from injection of botulin.

Adult↗
PubMed2001

Hepatic damage in C282Y homozygotes relates to low numbers of CD8+ cells in the liver lobuli.

BACKGROUND: Although most Caucasian patients with hereditary haemochromatosis (HH) show the same mutation in the HFE gene, the phenotypic expression of the disease varies greatly. We have previously shown that patients with HH who have high iron stores have low numbers of circulating CD8+ T lymphocytes. PATIENTS AND METHODS: Liver and peripheral blood were studied in 37 C282Y homozygous HH patients; nine normal livers and 11 livers from patients with cirrhosis due to hepatitis C virus or alcoholic liver disease were also investigated. Eleven jejunal biopsies from HH patients and 17 normal biopsies were studied. The numbers of CD8+ cells were determined in peripheral blood by fluorescence-activated cell sorting analysis, and in the liver or small intestine by immunohistochemistry. RESULTS: In HH patients the number of CD8+ T lymphocytes in peripheral blood correlated significantly with the number of CD8+ cells in the liver lobuli but not with that in the small intestine. Body iron stores correlated negatively with the number of CD8+ T lymphocytes in peripheral blood and in the liver, but not with the number in the small intestine. HH patients with cirrhosis had the lowest CD8+ cell count in liver sections, in contrast with other forms of cirrhosis. CONCLUSION: The results indicate that HH patients with the HFE C282Y mutation and low numbers of CD8+ cells in the liver lobuli have higher iron stores and are more prone to develop liver cirrhosis.

Adult↗
PubMed2001

Low headache prevalence amongst women with high TSH values.

The aim of this large cross-sectional population-based study was to examine a possible positive or negative association between thyroid dysfunction and headache. Between 1995 and 1997, all 92 566 adults in Nord-Trøndelag County in Norway were invited to participate in a health survey. A total of 51 383 (56%) responded to a headache questionnaire, whereof thyroid-stimulating hormone (TSH) was measured in 28 058 individuals. These included 15 465 women and 8019 men above 40 years of age, 1767 randomly selected individuals between 20 and 40 years of age, and 2807 (97%) with thyroid dysfunction. Associations between thyroid dysfunction and headache were assessed in multivariate analyses, estimating prevalence odds ratios (OR) with 95% confidence intervals (CIs). High TSH values were associated with low prevalence of headache. This was most evident amongst women with no history of thyroid dysfunction. Amongst these, headache was less probable (OR=0.5, 95% CI 0.3-0.7) if TSH > or = 10 mU/l than in women with normal TSH (0.2-4 mU/l). In all age groups between 40 and 80 years, TSH was lower amongst headache sufferers, especially migraineurs, than in those without headache complaints.

Adult↗
PubMed2000

Head-HUNT: validity and reliability of a headache questionnaire in a large population-based study in Norway.

We have assessed the validity and reliability of a self-administered headache questionnaire used in the 'Nord-Trøndelag Health Survey 1995-97 (HUNT)' in Norway, by blindly comparing questionnaire-based headache diagnoses with those made in a clinical interview of a sample of the participants. Restrictive questionnaire-based diagnostic criteria for migraine, assessed according to modified criteria of the International Headache Society, performed excellently in selecting 'definite' migraine patients (100% positive predictive value). The best agreement concerning migraine diagnoses was achieved by using a liberal set of criteria (kappa 0.59). Similar agreement was found evaluating patient status as headache sufferers, and as sufferers from frequent headaches (>6 days per month) (kappa 0.57 and 0.50, respectively). The kappa values of non-migrainous headache and chronic headache (> 14 days per month) were 0.43 and 0.44, respectively. The results suggest that our self-administered questionnaire may be suitable in identifying a population with 'definite' migraine, and the questionnaire is an acceptable instrument in determining the prevalence in Nord-Trøndelag of headache sufferers, migraine, non-migrainous headache, and frequent or chronic headache sufferers.

Confidence Intervals↗
PubMed2000

Prevalence of migraine and non-migrainous headache--head-HUNT, a large population-based study.

The objective of this study was to estimate the 1-year prevalence of the following categories of headache; migraine, non-migrainous headache, frequent headache (>6 days/month), and chronic headache (>14 days/month). Between 1995 and 1997, all 92,566 inhabitants 20 years and older in Nord-Trøndelag county in Norway were invited to a comprehensive health study. Out of 64,560 participants, a total of 51,383 subjects (80%) completed a headache questionnaire. The overall age-adjusted 1-year prevalence of headache was 38% (46% in women and 30% in men). The prevalence of migraine was 12% (16% in women and 8% in men), and for non-migrainous headache 26% (30% in women and 22% in men). For frequent headache (> 6 days per month) and for chronic headache (>14 days per month), the prevalence was 8% and 2%, respectively. Women had a higher prevalence than men in all age groups and for all headache categories. Prevalence peaked in the fourth decade of life for both men and women, except for 'frequent non-migrainous headache', which was nearly constant across all age groups in both genders. In accordance with findings in other western countries, we found that headache suffering, including migraine, was highly prevalent, especially in younger women.

Adult↗
PubMed2000

[Radiocarpal fracture dislocation].

Radiocarpal fracture dislocation is a very rare, often complex injury and the result of high energy trauma. We present a retrospective review of four patients. The injury in our series was characterized by a complete dorsal dislocation of the radiocarpal joint with fracture of the radial styloid, associated with avulsion of the palmar and dorsal cortical margin of the distal radius (radiotriquetral ligament included). One case presented a die punch fracture, another case a partial lesion of the scapholunate ligament. All injuries were immediately treated by closed reduction in local anaesthesia. All patients underwent operative treatment with a dorsal approach within seven days. The radial styloid was fixed with screws or Kirschner-wire, the impaction of the dorsoulnar aspect of the radius with elevation and fixation with a 2.7 mm plate. The tear of the scapholunate ligament was sutured and stabilized with Kirschner-wire between scaphoid and lunatum. All wrists were immobilized with a forearm cast for four weeks. The mean follow-up was 25 months. At the time of follow-up all patients showed a very good functional outcome, although the radiographic analysis revealed some osteoarthrotic changes.

Adult↗
PubMed1999

Differential regulation of mitogen-activated protein kinases by microtubule-binding agents in human breast cancer cells.

Drug design targeted at microtubules has led to the advent of some potent anti-cancer drugs. In the present study, we demonstrated that microtubule-binding agents (MBAs) taxol and colchicine induced immediate early gene (c-jun and ATF3) expression, cell cycle arrest, and apoptosis in the human breast cancer cell line MCF-7. To elucidate the signal transduction pathways that mediate such biological activities of MBAs, we studied the involvement of mitogen-activated protein (MAP) kinases. Treatment with taxol, colchicine, or other MBAs (vincristine, podophyllotoxin, nocodazole) stimulated the activity of c-jun N-terminal kinase 1 (JNK1) in MCF-7 cells. In contrast, p38 was activated only by taxol and none of the MBAs changed the activity of extracellular signal-regulated protein kinase 2 (ERK2). Activation of JNK1 or p38 by MBAs occurred subsequent to the morphological changes in the microtubule cytoskeleton induced by these compounds. Furthermore, baccatine III and beta-lumicolchicine, inactive analogs of taxol and colchicine, respectively, did not activate JNKI or p38. These results suggest that interactions between microtubules and MBAs are essential for the activation of these kinases. Pretreatment with the antioxidants N-acetyl-L-cysteine (NAC), ascorbic acid or vitamin E, blocked H2O2- or doxorubicin-induced JNKI activity, but had no effect on JNKI activation by MBAs, excluding a role for oxidative stress. However, BAPTA/AM, a specific intracellular Ca2+ chelator, attenuated JNK1 activation by taxol but not by colchicine, and had no effect on microtubule changes induced by taxol. Thus, stabilization or depolymerization of microtubules may regulate JNK1 activity via distinct downstream signaling pathways. The differential activation of MAP kinases opens up a new avenue for addressing the mechanism of action of antimicrotubule drugs.

Apoptosis↗
PubMed1998

[Myelin diseases affecting both the central and the peripheral nervous system].

Myelin is synthesized by oligodendrocytes in the central nervous system and by Schwann cells in the peripheral nervous system. A combined dysmyelinating/demyelinating process in the central nervous system and in the peripheral nervous system occurs only rarely. A brief review of these conditions is given in this article. Occasionally, coexistence of multiple sclerosis and chronic inflammatory demyelinating polyneuropathy is reported. Cases of multiple sclerosis, hypertrophic polyneuropathy, and central nervous system demyelination in Miller-Fisher syndrome and Guillain-Barré syndrome have also been reported. Concurrent dysmyelination in the central nervous system and peripheral nerve demyelination are common in metachromatic leukodystrophy, Krabbe disease and adrenoleukodystrophy. A Norwegian family with adult-onset demyelinating disease affecting both the peripheral and central nervous system has recently been described. The mode of inheritance is probably autosomal dominant, but its exact nature remains unknown.

Central Nervous System Diseases↗
PubMed1998

[Defective iron metabolism in genetic hemochromatosis. The mechanisms remain unknown in spite of genetic advances].

Genetic haemochromatosis (GH) is one of the most common hereditary diseases, with a prevalence of 1-5/1000 in the Western world. In 90 per cent of cases a mutation is found in an MHC-class-like gene designated HFE, involving a substitution at position 282 of the HFE protein and resulting in defective binding of beta(2)-microglobulin. Animals with beta(2)-microglobulin deficiency develop iron overload, indicating this protein to be involved in the regulation of iron metabolism. Hepatic iron overload results in increased production of oxygen free radicals and peroxidation of membrane lipids, thus causing damage to lysosomes, mitochondria and the endoplasmic reticulum. These cellular events may progress to cell death, fibrogenesis, and the development of liver cirrhosis which is associated with a 200-fold increase in risk of hepatocellular carcinoma. In addition to the risk of diabetes, arthralgia, cardiac arrhythmia, pituitary insufficiency and hypogonadism, iron excess is also associated with aggravation of the cytotoxic effects exerted on hepatocytes by other agents such as alcohol or hepatotrophic viruses. The treatment of iron overload in GH consists of weekly venesection until the serum ferritin level is normalized, followed by maintenance therapy. Survival rates are normal if the disease is detected and treated before complications have developed.

Diagnosis, Differential↗
PubMed1998

[Hereditary autosomal dominant brain infarction].

Some aspects of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are reviewed. The condition causes stroke and vascular dementia. Pathological examination reveals multiple small, deep infarcts, leukoencephalopathy, and non-atherosclerotic, non-amyloid angiopathy which mainly involve the small cerebral arteries where there are severe alterations in vascular smooth-muscle cells. In hereditary autosomal dominant stroke condition patients with mutations in the human Notch 3 gene on chromosome 19 have been identified. Skin and muscle biopsy may be useful for diagnosing this condition. No causal treatment is available. Hereditary autosomal dominant stroke condition has not been diagnosed in any Norwegian family to date.

Adult↗
PubMed1998

Progressive central and peripheral demyelinating disease of adult onset in a Norwegian family.

OBJECTIVE: To describe the clinical features of a Norwegian family with a combined central and peripheral demyelinating disease. DESIGN: Multiple case report. SUBJECTS AND MATERIALS: Three generations of a Norwegian family. Medical records were available for all 9 members of the second generation and 5 affected members in the third generation. RESULTS: At least 5 members had clinical features, neuroimaging findings, and electrophysiologic signs indicating a chronic progressive disorder affecting both the central and peripheral nervous systems. The clinical symptoms developed between the ages of 30 and 70 years in affected family members, who gradually developed sensory loss, muscle deterioration, and distal weakness in all extremities, unsteady gait, and dysarthria. Five of 9 persons in the second generation had strokes and experienced mental deterioration. The initial stroke episodes were recognized between the ages of 54 and 68 years, and death occurred between the ages of 62 and 75 years. In 7 subjects, cerebrospinal fluid protein levels were increased, and in 5 agar gel electrophoresis indicated blood-brain barrier dysfunction. Seven family members had neuroimaging signs of a widespread white matter disorder. In 4 subjects, neurophysiological investigations indicated a polyneuropathy, and in 3 subjects, results from a sural nerve biopsy showed a demyelinating neuropathy. There was no evidence of co-inheritance with genetic markers of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (19p), PMP22 (17q), APP (21q), CMTX1 (Xq), or PLP (Xq). CONCLUSIONS: Progressive central and peripheral demyelinating disease seems to be a distinct type of hereditary adult-onset demyelinating disorder affecting both the peripheral and central nervous systems. Its exact nature remains unknown.

Adult↗
PubMed1998

HFE mutations in patients with hereditary haemochromatosis in Sweden.

OBJECTIVE: To determine the frequency of mutations (C282Y and H63D) in a newly identified gene HFE in patients with hereditary haemochromatosis (HH) in Sweden. DESIGN: Molecular genetic analyses of the HFE gene (polymerase chain reaction (PCR) followed by enzyme restriction) were performed in genomic DNA from unrelated patients with a clinical diagnosis of HH and in healthy subjects. SETTINGS: Patients with HH treated with phlebotomies at Karolinska Hospital and Huddinge Hospital were analyzed. SUBJECTS: Eighty-seven unrelated patients with HH and 117 healthy controls. RESULTS: It was found that the HFE C282Y mutation occurs in 94.2% of chromosomes from patients with HH. Eighty patients (92.0%) were homozygous for the C282Y mutation and one was heterozygous. Three patients were heterozygous for both C282Y and H63D mutations. One patient was homozygous and one was heterozygous for the H63D mutation. One patient carried normal alleles. In healthy controls, the C282Y mutation occurred in nine subjects (7.7%), all of which were heterozygous. The H63D mutation was found in 28 control subjects, one of which was homozygous. CONCLUSIONS: We found that the majority of patients with HH have the C282Y mutation in the HFE gene. The frequency of the H63D mutation was higher in controls than in patients with HH, although in chromosomes at risk the frequency of the H63D mutation was higher in patients.

Adult↗
PubMed1996

p53 modulation of anchorage independent growth and experimental metastasis.

Death in circulation is one of the natural barriers preventing dissemination of tumor cells and formation of metastases. One of the negative factors acting in circulation is the loss of cell contact with natural substrate which can be imitated in vitro by the incubation of cells in suspension or in semi-solid media. Normal mouse fibroblasts (MEFs) stay viable in suspension and undergo p53-independent G1 growth arrest. Transformation with Ela and ras oncogenes leads to the abrogation of this arrest and to the p53-dependent apoptosis occurring in G1 phase of the cell cycle. Suppression of apoptosis by p53 gene knock-out, transduction of dominant negative p53 mutant or bcl-2 prevents death in suspension and greatly induces frequency of colony formation in semi-solid media. The ability of cells to undergo apoptosis does not correlate with their tumorigenicity in nude mice but does correlate with their ability to survive in lungs of intravenously injected mice and to form experimental metastases. We suggest that abrogation of a p53-mediated apoptosis facilitates experimental metastasis by promoting survival of tumor cells in circulation.

Animals↗
PubMed1996

Hepatotoxicity induced by iron overload and alcohol. Studies on the role of chelatable iron, cytochrome P450 2E1 and lipid peroxidation.

BACKGROUND/AIMS: Clinical experience and studies with experimental animal models indicate a synergistic hepatotoxic effect of dietary iron overload and chronic alcohol ingestion. In order to elucidate the mechanism underlying this synergism, we examined the hepatic levels of ethanol-inducible cytochrome P450 2E1, glutathione and malondialdehyde, and the effect of iron chelation with desferrioxamine, in livers from rats treated with iron and/or ethanol. METHODS: Animals received diets with or without 2.5-3% carbonyl iron for 6-9 weeks, followed by an ethanol-containing diet or a liquid control diet for 5-9 weeks. Desferrioxamine was administered subcutaneously with mini-osmotic pumps. Alanine aminotransferase activity in serum and hepatic contents of glutathione and malondialdehyde were determined. The hepatic level of cytochrome P450 2E1 was determined with Western Blotting using a specific polyclonal antibody. RESULTS: The combination of iron and alcohol led to a marked increase in serum alanine aminotransferase activity as compared with all other treatment groups, and iron chelation with desferrioxamine reversed these increases. Treatment with alcohol alone led to slightly increased aminotransferases compared with controls. The level of cytochrome P450 2E1 was significantly elevated in microsomes isolated from ethanol-treated rats, but neither additional iron supplementation nor desferrioxamine influenced this level significantly. Glutathione contents were increased in the livers of animals treated with iron and/or ethanol. Malondialdehyde values were increased in iron-treated animals, whereas neither ethanol nor desferrioxamine altered malondialdehyde levels significantly. CONCLUSIONS: The toxic effects exerted by the combination of iron overload and chronic ethanol feeding on rat liver are dependent on a pool of chelatable iron. The hepatic level of cytochrome P450 2E1 is markedly induced by ethanol but not further altered by iron overload. Neither increased lipid peroxidation nor depletion of hepatic glutathione levels can explain the synergistic hepatotoxic effects of iron and ethanol in this model.

Alanine Transaminase↗
PubMed1996

Usefulness of flow cytometric detection of cell surface interleukin-6 receptors in human myeloma cell lines.

A flow cytometric procedure was used to analyse the cell surface interleukin-6 receptor (IL-6R) based on the principle of detecting the binding of IL-6 to IL-6R. The bound IL-6 was visualized by reacting with anti-IL-6 antibody, a second biotinylated antibody to immunoglobulins, fluorescein-conjugated avidin and biotinylated, fluorescein-conjugated bovine serum albumin. Studies with a number of human myeloma cell lines showed that the fluorescence signal from cellular binding of IL-6, and thus IL-6R, could be specifically discerned from the background. The specific IL-6R signal could be semi-quantitatively expressed as the mean channel number of the fluorescence histogram or as relative IL-6R density in relation to a reference cell line, such as U266-BL cells. The relative IL-6R density of various myeloma cell lines thus determined was found to correlate with their sensitivity to the growth inhibitory effect of glucocorticoids in vitro. Quantitatively, calibration of the staining procedure with microbeads that have a defined binding capacity for anti-IL-6 antibody allowed calculation of cellular IL-6R density that yielded results close to that reported with conventional radio-ligand binding assay. Similarly, the cytometric method was applied to the studies of kinetics of IL-6/IL-6R interaction and the cellular IL-6R changes after ligand-binding to provide estimates of IL-6R binding affinity and IL-6R turnover rate. It is suggested that flow cytometric measurement of cellular IL-6R is useful in providing biologically relevant information on myeloma cells.

Antigens, CD↗