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Biomedical subjects

O Andersen

Publications and source records attributed to O Andersen.

At least 91 records · Page 5Linked to original sources
PubMed1994

[Familial aggregation of insulin-dependent diabetes mellitus in Denmark. A nation-wide population study].

This study aimed to assess the prevalence of familial aggregation of insulin-dependent diabetes mellitus (IDDM), among Danish families with a diabetic child and to compare epidemiological data for familial and sporadic cases of IDDM children. All IDDM patients aged 19 years or less treated at paediatric departments or departments of internal medicine were identified and asked to complete a questionnaire regarding diabetes onset and family history. Of 1574 probands identified, 1419 participated (90.2%). Additional cases of IDDM were found in 12.8% of the families. Among these families, in 6.8% the father and in 2.1% the mother were diabetics and in 5.0% at least one of the siblings were diabetics. In familial cases the proband was significantly younger at diabetes onset, the parents were younger at birth of the IDDM child and no differences in gender were observed in contrast to sporadic cases, where more males were found. Thus, heterogeneity in epidemiological characteristics was observed between familial and sporadic cases.

Adolescent↗
PubMed1994

Automatic sequencing of mitochondrial tRNA genes in patients with mitochondrial encephalomyopathy.

We have investigated nine children with infantile onset of mitochondrial myopathy and two adults with myoclonus epilepsy and ragged-red fibers (MERRF) and chronic progressive external ophthalmoplegia (CPEO), respectively. These patients lacked any of the previously known pathogenic tRNA mutations. Southern blot analysis of muscle mtDNA revealed no deletions. The tRNA genes of muscle mtDNA were sequenced. Restriction enzyme analysis of PCR fragments was performed to verify the presence of the mutations identified by automatic sequencing. Several tRNA mutations were found, but they were all homoplasmic. Furthermore, the mutations were either present in controls or did not change nucleotides conserved between species. This strongly suggests that none of the tRNA mutations identified in the 11 patients with mitochondrial encephalomyopathy was pathogenic. It can thus be concluded that mitochondrial tRNA mutations and mtDNA deletions probably are an infrequent cause of mitochondrial disorders in infants. Patients with MERRF and CPEO may lack both pathogenic point mutations of tRNA genes and deletions of mtDNA.

Adult↗
PubMed1994

[Meningitis].

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Child↗
PubMed1994

The microvascular changes in cases of hereditary multi-infarct disease of the brain.

A report on a cerebro-vascular disease with autosomal dominant inheritance, characterised by stroke-like episodes beginning in early adulthood and progressive dementia, afflicting one family living in Sweden was presented in 1977. Another afflicted member showing gait and coordination disturbances and impaired cognitive functions is now introduced. Magnetic resonance imaging revealed multiple brain lesions indicating ischaemic injuries. Previous autopsy studies of other cases revealed white matter atrophy, multiple infarcts and lacunes. In one patient who had died from a cerebral haemorrhage, obliteration of intracerebral arteries, occasionally with organised thrombi was present. Autopsy material has now been reinvestigated with special attention to changes of intracerebral arterioles. Cases with long duration of the disease presented pronounced fibrous thickening of the wall of numerous intracerebral arterioles, degeneration of smooth muscle cells of the media and obliteration of the lumen. Immunohistochemistry showed marked expression of fibrillary collagen types I, III and V and of the basal lamina components collagen type IV and laminin. These depositions are probably induced by some primary dysfunction of smooth muscle cells or endothelial cells. Perivascular reactive astrocytes with endothelin-1-like immunoreactivity were present in some brain regions. Endothelin-1 is the most powerful vasoconstrictor peptide known to date. Structural remodelling of intracerebral arterial vessels, actions of different vasoactive factors and rheological disturbances may all interfere with local blood flow in this disease and cause the parenchymal changes of the brain.

Adult↗
PubMed1994

Human spumaretrovirus antibody reactivity in multiple sclerosis.

The role of human spumaretrovirus (HSRV) infections in the pathogenesis of multiple sclerosis (MS) was investigated with recombinant HSRV env-specific enzyme-linked immunosorbent assay. The presence of HSRV antibodies was determined in pairs of serum and cerebrospinal fluid (CSF) samples from 60 MS patients. In 7 of these patients serial serum and CSF samples were obtained in relation to the clinical activity of the disease during a period of 2 years. No increased antibody reactivity was demonstrable in the MS population compared with 14 aseptic meningitis patients, 50 blood donors and 16 healthy controls. Slightly elevated levels of antibodies were demonstrable in serum and/or CSF in 4 MS patients but also in 1 patient with aseptic meningitis, 1 blood donor and 1 child. No marked serum or CSF HSRV antibody fluctuation was observed in the MS patients followed longitudinally. Thus, this study does not support the involvement of HSRV in the pathogenesis of MS.

Adolescent↗
PubMed1994

Prediction of outcome in multiple sclerosis based on multivariate models.

An incidence cohort of 308 multiple sclerosis patients was followed up repeatedly during at least 25 years of disease. In the patients with acute onset, multivariate survival analyses were performed and predictive models created. The endpoints DSS 6 and start of progressive disease were used. A number of variables were tested. The most important of these for prediction and therefore included in these models were: age at onset, sex, degree of remission after relapse, mono- or polyregional symptoms, type of affected nerve fibres, number of affected neurological systems. The relapse rate did not correlate with prognosis. In the predictive models, coefficients and risk ratios are provided that can be used for calculating the risk of progression and DSS 6 or to predict the median time for these endpoints in individual patients. It was also found that the risk of progression is not constant, but has a maximum a certain time after disease onset. For a patient with early onset, the risk is low in the beginning, but reaches a maximum level, which is several times higher, after about 15 years. The patient with a late onset has a much higher risk of endpoint immediately after onset, but reaches the maximum in a few years, and after that the risk decreases.

Acute Disease↗
PubMed1994

HLA and prognosis in multiple sclerosis.

The patients of a multiple sclerosis (MS) incidence cohort with 25 years of longitudinal follow-up were typed for HLA-DR and DQ. This type of cohort provides reliable data for gene frequencies and prognostic studies. The influence of sampling bias, mainly due to mortality during the long follow-up, was accounted for. A positive association between MS and DR15,DQ6 was confirmed, but this haplotype did not influence prognosis. There was no difference in haplotype frequency between relapsing-remitting and primary chronic progressive MS. DR17,DQ2 was significantly over-represented in the quartile with the most malignant course. The haplotype DR1,DQ5, which was found rather less frequently in MS patients, also tended to be associated with a poorer prognosis.

Aged↗
PubMed1994

Evaluation of mercury in hair, blood and muscle as biomarkers for methylmercury exposure in male and female mice.

Recently established reference intervals demonstrate that blood mercury is significantly higher in women than in men. Mercury in blood and hair are both used as biomarkers for human methylmercury exposure and employed in risk assessment without considering possible sex-related differences in toxicokinetics of methylmercury. In an experimental study using male and female mice of three different strains, the validity of mercury in hair, blood and muscle as indicators of methylmercury exposure was evaluated. Significant sex-related differences in the toxicokinetics of methylmercury were observed in the mice and it is concluded that hair and blood levels of mercury are of questionable relevance as indicators of both body burden and target organ concentrations of mercury. However, blood concentrations might be used as an indicator of brain deposition and the correlation improves after corrections due to sex-related differences in toxicokinetics.

Adipose Tissue↗
PubMed1994

Effect of tetraethylthiuramdisulphide and diethyl-dithiocarbamate on nickel toxicokinetics in mice.

A new experimental pharmacokinetic model using the gamma-emitting isotope 57Ni for studying nickel toxicokinetics was employed in a recent investigation (Nielsen et al. 1993) in order to quantitatively study, for the first time, the effect of tetraethylthiuram disulphide (disulfiram, Antabuse, TTD) and sodium diethyldithiocarbamate (DDC) on whole-body retention and organ distribution of nickel in mice. TTD or its decomposition product DDC given orally by stomach tube shortly after oral administration of a low dose of nickel chloride labelled with 57Ni resulted in an approximately ten times higher whole-body retention of nickel compared to the retention in a control group exposed to nickel only. These chelators increased the whole-body retention of nickel also when given by intraperitoneal injection shortly after oral or intraperitoneal administration of nickel. Oral administration of a single dose of TTD or DDC rapidly after an oral dose of nickel chloride also resulted in extensive changes in the organ distribution of nickel, thus the nickel content in the brain was at least 700 times higher than in a control group given the same dose of nickel only. If DDC was given intraperitoneally after nickel given orally, the relative organ distribution of nickel to most organs was the same as if the chelator was given orally, though the contents of the liver and lungs were lower. That TTD and DDC resulted in a transport of nickel to the brain, is underlined by the fact that after 20 hr, approximately 15% and after 45-50 hr, 30% of the total body burden of Ni was found in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Calcium-enhanced aggregation of serum amyloid P component and its inhibition by the ligands heparin and heparan sulphate. An electron microscopic and immunoelectrophoretic study.

Serum amyloid P component (SAP) is a pentraxin found in the circulation and in all forms of amyloid deposits. Its physiological and pathophysiological functions are largely unknown. Electron microscopy showed purified human SAP to consist of double pentameric discs compatible with the results of size chromatography. The formation of double pentamers did not require calcium ions. The outer diameter of the discs arranged face-to-face was 11.6 nm and the inner diameter 3.2 nm. The thickness of single and double pentamers was 4.1 and 8.7 nm, respectively. Quadruple pentamers were occasionally seen. The self-aggregation of human SAP molecules was investigated in the presence and absence of calcium ions at different concentrations. In calcium-free solutions few and mostly small SAP aggregates were seen. After addition of calcium at increasing concentration the aggregates grew in size and crystalline-like structures were formed already at 2 mM calcium. At 25 mM calcium, large aggregates with a crystalline array occasionally exhibiting cylinders predominated. Binding of the ligands heparin and heparan sulphate to SAP completely abolished the calcium-enhanced aggregation, but the distribution of the SAP molecules was affected, resulting in strands or groups of adjacent molecules. The electrophoretic mobility of SAP was moreover significantly altered after its calcium-dependent reaction with these ligands. We conclude that purified SAP has a tendency to double pentamer formation and self-aggregation also in the absence of calcium ions. However, aggregation is greatly enhanced even at low concentrations (2 mM) of calcium. SAP's tendency to self-aggregation is abolished after its binding to heparin or heparin sulphate. Furthermore, our TEM studies indicate that purified human SAP freed of its natural ligands has the double pentameric form, whereas the electrophoretic investigations suggest that SAP's interaction with low-molecular-weight natural ligands in serum prevents homodimerization and self-aggregation.

Blotting, Western↗
PubMed1994

Experimental localization of intestinal uptake sites for metals (Cd, Hg, Zn, Se) in vivo in mice.

The intestinal uptake process consists of two separable steps: transport over the luminal membrane into epithelial cytoplasm and transport over the basolateral membrane into serosal fluid. A compound's residence time in mucosal epithelial cytoplasm depends on rates of the two transport processes and, if the rate of the second step is low, on the rate of mucosal sloughing. Using gamma-emitting metal isotopes, in vivo labeling profiles of the intestinal tract were obtained from mice eating their normal diet. The results pertain to processes in the functioning, undisturbed intestinal tract. Single-dose chase experiments indicated that intestinal uptake processes were in fact studied. The labeling profiles varied considerably for different metals. Thus, Cd++ was absorbed mainly in duodenum and early jejunum, while Zn++ was taken up in jejunum and ileum. The uptake profile of Hg++ indicated most rapid uptake in proximal jejunum. Selenomethionine labeled the entire intestinal tract, most rapidly the duodenum, the following intestinal segments were labeled with falling rate. This experimental method is rapid and simple. Further studies aim at developing a quantitative model suited for studying interactions between essential and toxic metals at the level of intestinal metabolism.

Animals↗
PubMed1994

Dose and time relations in Hg(++)-induced tubular necrosis and regeneration.

Mercuric chloride is a well-known human and animal nephrotoxicant. Previous studies have demonstrated an inverse relationship between dose size and relative whole-body retention of mercury after oral administration of mercuric chloride to mice. The present study indicates that this inverse relationship is caused by a dose-related induction of kidney damage leading to increasing leakage of mercury through the kidneys. Histopathologic investigation revealed extensive necrosis of the proximal tubules in kidneys from mice exposed to 100 mumole HgCl2/kg or higher doses. Moreover, maximum renal damage occurred between days 2 and 3 after administration. The renal damage was followed by regeneration, which was observed between days 3 and 7 at increasing dose levels up to 100 mumole HgCl2/kg. The amount of glutathione and the glutathione peroxidase activity in kidney decreased with increasing doses of mercuric chloride. The reduced glutathione peroxidase activity was due to a reduction in selenium-dependent glutathione peroxidase activity. The level of lipid peroxidation was not changed by increasing doses of mercuric chloride, and hence was not a primary toxic mechanism in acute nephrotoxicity induced by mercuric chloride.

Animals↗
PubMed1994

Effects of simultaneous low-level dietary supplementation with inorganic and organic selenium on whole-body, blood, and organ levels of toxic metals in mice.

Classical experiments have demonstrated that Se compounds protect against the toxicity of several toxic metals in acute experiments with simultaneous parenteral administration of high doses of Se and the toxic metal. Blood and organ levels of the toxic metals were increased, conceivably due to formation of inert Se complexes. Less is known about effects of long-term Se status on the toxicokinetics of toxic metals. Possible Se interactions in toxic metal biokinetics should therefore be studied at Se levels ranging from those just sufficient to avoid Se deficiency and up to those believed to be optimum in relation to antioxidative and other beneficial effects of Se. The toxic-metal exposure levels investigated should be similar to those occurring in human populations that are not occupationally exposed. To study interactions between Se and toxic metals at ultralow exposure levels, mice were fed semisynthetic diets containing different levels of Se. The mice were given ultralow doses of metal salts either as a single oral dose by stomach tube or as prolonged exposure in the drinking water. Diets with high or normal Se levels slightly, but nonsignificantly increased the whole-body retention (WBR) of Hg++ and CH3Hg+ compared to a diet low in Se. The dietary Se level was, however, without effect on the WBR of Cd2+ and Ag2+ in single-dose experiments. During prolonged exposure, the diets fortified with Se increased the WBR of Ag2+, had no effect on WBR of Hg2+, and reduced the WBR of CH3Hg+ and Cd2+. During prolonged exposure, the diets fortified with Se reduced blood Hg++ while organ levels were unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Incidence of juvenile thyrotoxicosis in Denmark, 1982-1988. A nationwide study.

The objective of this study was to ascertain the annual incidence density of thyrotoxicosis in children under the age of 15 years in Denmark in 1982-1988. The design was based on computerized hospital registration of patient admittances in all departments of paediatrics and internal medicine of Denmark (Faroe Islands and Greenland excluded). Fifty-six children (48 girls and 8 boys) had a confirmed diagnosis of thyrotoxicosis, giving a national incidence density of 0.79/100,000 person-years. In children aged 0-4 years the incidence was very low (0.1/100,000), with no sex difference. In boys aged 5-9 years a similar low incidence was found, while in boys aged 10-14 years the incidence increased to 0.48/100,000. In girls aged 5-9 years the incidence increased to 0.96/100,000, reaching a maximum of 3.01 in the 10-14-year-old girls. In children of > 4 years of age a female preponderance of 6.7:1 was significant. It is concluded that thyrotoxicosis is a rare disorder in Danish children under the age of 15 years, and the incidence increases with age. Female preponderance is significant from early childhood.

Adolescent↗
PubMed1994

Spinal arteriovenous malformations. Health-related quality of life after embolization.

The overall function, pain and mood disturbances of 19 patients with spinal arteriovenous malformations (AVM), treated by embolization between 1983 and 1988, were studied. The after-care had taken place in different hospitals and clinics. The patients demonstrated markedly poorer physical function (Sickness Impact Profile) and poorer psychological well-being (Mood Adjective Check List) than control population samples and a comparison group of traumatic incomplete paraplegics. The degree of decrease of mood levels implied possible depressive disorder (Hospital Anxiety and Depression scale) in 16% of the patients and differed from that of the paraplegic comparison group. Furthermore, the AVM patients reported more disturbance of their family and social life than the paraplegics and they were more seldom gainfully employed. Patients recorded a wide range of pain scores, significantly worse than the paraplegics, and their pain was closely linked to overall quality of life (QL) perception. The QL scores were consistently related to all measures of functional and emotional status, but no connection with neurological lesion levels or medical complications was found. Specialised programmes after embolization, such as those offered in spinal injury units, would appear appropriate for AVM patients to improve their physical functioning and to provide a more rewarding social life.

Activities of Daily Living↗
PubMed1994

Hormone conference at Sahlgren's University Hospital: polycythemia and inappropriately high serum erythropoietin concentration in a 62-year-old man.

A 62-year-old man with a history of coronary insufficiency complained at his scheduled visit to the outpatient clinic of symptoms suggestive of gastritis. His blood hemoglobin concentration, however, was markedly increased. Results of a hematological work-up suggested an erythropoietin-producing tumor. Signs of increased intracranial pressure then led to the finding of a cerebellar tumor, which could explain his vertigo and abdominal symptoms. This cystic capillary hemangioblastoma probably was responsible for the erythropoietin production and also seemed to produce basic fibroblast growth factor. The clinical evaluation of polycythemia as well as erythropoietin biochemistry and clinical application are reviewed.

Capillaries↗
PubMed1993

Clinical improvement and amyloid regression after liver transplantation in hereditary transthyretin amyloidosis.

Familial amyloid polyneuropathy (FAP) is a fatal autosomal dominant disorder. Progressive peripheral and autonomic neuropathy are associated with neural and visceral deposition of amyloid, derived most commonly from the Met-30 variant of the plasma protein transthyretin. We have reported previously that orthotopic liver transplantation causes prompt replacement of variant transthyretin by the donor wild-type in the plasma. We now report clinical outcome 1-2 years after transplantation. Three of the first four patients have improved general wellbeing, walking ability, and bowel function, and one of them has regained normal bladder and bowel function. There has been little objective improvement in peripheral neuropathy. The fourth patient, who had the most severe neurological deficits and a complicated postoperative course, has not improved but there has been no further deterioration in contrast to the inexorable progression before transplantation. Quantitative scintigraphy with radiolabelled serum amyloid P component showed visceral amyloid deposits in all three patients studied; in two who were followed serially the deposits regressed after transplantation in association with the clinical improvement. Another FAP patient who was also monitored prospectively for 2 years but who did not undergo transplantation, showed, as expected, progression of neuropathy and increased visceral amyloid deposition. Liver transplantation does therefore have important benefits in FAP during the first 2 years after surgery. Neurological decline is halted and amyloid deposits can be mobilised. The best timing and long-term results of the procedure must now be established.

Adult↗