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Biomedical subjects

O Andersen

Publications and source records attributed to O Andersen.

At least 109 records · Page 6Linked to original sources

Prophylactic cranial irradiation increases the risk of testicular damage in adult males surviving ALL in childhood.

By combining three series of Scandinavian patients, we were able to compare the late testicular sequelae in 41 adult males whose therapy had included chemotherapy alone or chemotherapy with cranial irradiation without other radiotherapy for ALL in childhood. In multivariate analysis, cranial irradiation was associated with a decrease of 5.7 (95% confidence limits 1.5-9.9) cm (P = 0.010) in height, and a decrease of 4.8 (0.3-9.2) ml (P = 0.036) in testicle size. Cyclophosphamide was associated with increases of 8.2 (-0.5-16.9) (P = 0.065) and 3.9 (0.3-7.4) U/L (P = 0.036) in serum FSH and LH concentrations, respectively. Of the 12 patients who had received both cranial irradiation and cyclophosphamide therapy, 4 (33%) had delayed pubertal development as compared with 1 (3.5%) of the other 29 patients (P = 0.008). Patients 12-16 years of age at diagnosis had larger testicles (P = 0.051) and higher testosterone concentrations (P = 0.026) than others. Neither sexual activity nor semen findings correlated with the preceding treatment. Our data indicate that prophylactic cranial irradiation may be associated with impaired growth and pubertal development in boys with ALL.

Adolescent↗

Toxicokinetics of nickel in mice studied with the gamma-emitting isotope 57Ni.

The gamma-emitting isotope 57Ni was generated in a cyclotron to allow whole-body counting of laboratory animals dosed with nickel. 57NiCl2 was administered either orally by gastric intubation or by intraperitoneal injection to groups of mice in doses equivalent to the average human daily dietary nickel intake per mass unit. When given orally, the whole-body retention (WBR) was 0.02-0.36% of the administered dose at 45-75 hr. When given intraperitoneally, the WBR was 1-6% at 20-50 hr. After adjustment for the rapid excretion of systemic nickel, the intestinal absorption could be estimated to be 1.7-10%. The relative WBR did not vary with the magnitude of the dose within 0.05-5 mumol Ni/kg given orally or 0.005-0.5 mumol/kg given intraperitoneally. At 8 hr, the tissue concentration was highest in the kidneys, followed by the carcass, lungs, testicles, liver, and the spleen. After 20 hr, the highest concentrations were still found in the kidneys followed by the lungs, the liver, and the carcass. At 20 hr after oral administration, 50-70% of 57Ni retained in the body was within the carcass. The second highest nickel content was found in the kidneys, followed by the liver and lungs. Whereas nickel in the kidneys was rapidly excreted, the elimination from the lungs and liver was relatively slow, thereby, after 40 hr, resulting in a higher nickel content in the liver than that in the kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

A nationwide population-based study of the familial aggregation of type 1 (insulin-dependent) diabetes mellitus in Denmark. Danish Study Group of Diabetes in Childhood.

The objective of the present study was to assess the prevalence of familial aggregation of Type 1 (insulin-dependent) diabetes mellitus among Danish families with a diabetic child aged 20 years or less and to compare epidemiological data for familial and sporadic cases. We attempted to identify all patients with Type 1 diabetes aged 0-19 years in Denmark treated at paediatric departments or at departments of internal medicine. This comprises more than 98% of all patients with Type 1 diabetes in this age group. Patients were identified through the local diabetic out-patient registry and asked to complete a questionnaire regarding data on diabetes onset and family history. Of 1574 probands 1419 agreed to participate (90.2%). Additional cases of Type 1 diabetes were found in 171 families (12.8%). Of these 115 were parent-offspring affected families, and in 56 families at least two siblings had Type 1 diabetes and healthy parents. Significant correlation in age at onset of Type 1 diabetes in concordant siblings was observed (r = 0.5, p = 0.0004). Significantly more probands had an affected father with Type 1 diabetes than a mother affected (p < 0.0001). Heterogeneity in epidemiological characteristics was observed between familial and sporadic cases, i.e. familial index cases were younger at onset of the disease, their parents were younger at birth of the index case, and there was no difference in gender of familial cases in contrast to sporadic cases where significantly more males were found. Over a 4-year period (1986-1989) an increasing trend in incidence was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Peripheral neuropathy associated with monoclonal IgM antibody to glycolipids with a terminal glucuronyl-3-sulfate epitope.

Twenty-nine patients with paraproteinaemia, 12 with neuropathy and 17 without a previous record of neurological symptoms were clinically characterized. All 12 neuropathy patients had a moderate to severe sensorimotor demyelinating neuropathy. The patients were examined with regard to serum antibodies to gangliosides, including GM1, GD1a, GD1b, GT1b, and LM1, and other acidic glycolipids, including LK1 and sulphatide, of human brain and peripheral nerve. Sera from 80 blood donors, 40 men and 40 women 20-60 years of age, were used as normal controls. The sera were analysed with an ELISA performed on thin-layer chromatography plates. At a dilution of 1/400 none of the control sera gave a detectable reaction and a titre of > or = 1:400 was considered as a positive test. In 11 of the 12 neuropathy patients the paraproteinaemia was of IgM type and 10 of them had a positive antibody titre against LK1 and Hex-LK1, acidic glycolipids with a terminal glucuronyl-3-sulphate group. The antibody titre against LK1 in 1 patient was 1:400 and varied between 1:5,000 and 1:3,200,000 in the other 9. One of the patients also had a positive titre, 1:64,000, to sulphatide. None of the sera from the 17 paraproteinaemia patients without a previous record of neurological symptoms contained antibodies to LK1 or to any glycolipid antigen examined, except for sulphatide. A positive titre (> or = 1:400) of antibodies to sulphatide was found in sera from 4 of these patients, the titres being < or = 3,200.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Viral infections trigger multiple sclerosis relapses: a prospective seroepidemiological study.

A neurological surveillance was combined with prospective recording of upper respiratory and gastrointestinal infections and serological diagnosis of five common viral infections in 60 benign multiple sclerosis patients, with a mean follow-up of 31 months. During 4-week at risk (AR) periods encompassing common infections, a significant excess of MS relapses was found in the AR period, with a relative risk of 1.3. A seasonal variation of the MS relapse rate was found with a minimum in summer. There was a significant correlation between the number of AR relapses and the number of common infections per month explaining the periannual distribution of relapses. The non-AR relapses showed no seasonal variation. There was a significant correlation between adenovirus CF titre rises associated with upper respiratory infections and the occurrence of a major MS relapse in the AR period (n = 7), while influenza infections were not followed by a major MS relapse (n = 6). Linear homologies have been demonstrated between adenovirus and basic myelin protein. The epidemiological approach is essential to our understanding of systemic antigens triggering multiple sclerosis activity.

Adult↗

Susceptibility to demyelinating polyneuropathy in plasma cell dyscrasia may be influenced by amino acid position 9 of the HLA-DR beta chain.

Fifty-five patients with plasma cell dyscrasias were investigated by genomic typing for HLA-DR and -DQ genes by restriction fragment length polymorphism, neurophysiology and for presence of anti-myelin-associated glycoprotein (MAG) antibodies. In 26 patients, a polyneuropathy (PN) of demyelinating type was established. Among these individuals, an association was found with the presence of a tryptophan amino acid residue at position 9 of the DR beta chain (P < 0.01). This position is part of the first hypervariable region of the DR beta chain, and may be of importance in determining preferential peptide-binding capacity of the HLA-DR molecule. The presence of anti-MAG antibodies in 15 out of 17 patients with an IgM M-component and demyelinating PN (14 of these 15 individuals carrying a tryptophan at position 9) supports the pathogenic role of an autoimmune response against MAG. The finding of an HLA class II association may indicate a pathogenic role of T cell immunity in this condition.

Adult↗

Estrogen receptor binds to the salmon GnRH gene in a region with long palindromic sequences.

Footprinting and gel shift assays demonstrated that the human estrogen receptor (hER) specifically binds to two estrogen response element (ERE)-like motifs in the gonadotropin releasing hormone (GnRH) gene promoter region of Atlantic salmon (Salmo salar). The two ER binding sites are situated approximately 1.5 kb upstream of the transcriptional start site of the GnRH gene and are localized 49 bp from each other. Each ERE-like motif is composed of two palindromic ERE half-sites interspaced by 8 and 9 nucleotides, respectively. The salmon GnRH gene promoter region contains an almost perfect 426-bp-long palindromic sequence that might form a cruciform structure.

Animals↗

Prognostic factors in a multiple sclerosis incidence cohort with twenty-five years of follow-up.

An incidence cohort consisting of 308 multiple sclerosis patients was followed up repeatedly during at least 25 years of disease. A number of clinical factors were analysed with respect to their validity in assessing the long-term prognosis. Of the onset characteristics, the type of course was the most important, with primary progressive patients experiencing a much more severe course. In patients with an acute onset, low onset age, high degree of remission at first exacerbation, symptoms from afferent nerve fibres and onset symptoms from only one region (as compared with polyregional symptoms) of the central nervous system, were factors significantly associated with a favourable long-term prognosis. Of factors known 5 years after onset, a low number of affected neurological systems, a low neurological deficit score and a high degree of remission from the last bout were the most important favourable prognostic factors.

Cohort Studies↗

Possible association of HTLV-I infection and dementia.

We report a Swedish patient with progressive dementia possibly associated with human T cell-lymphotropic virus type I (HTLV-I) infection. The clinical investigation revealed no typical sings of other neurological disorders. The patient was probably infected in East-Asia 35 years before onset of the disease. High titers of specific HTLV-I antibodies were detectable with solid-phase peptide ELISA in serum (1:1.600) and cerebrospinal fluid (CSF) (1:20), and the CSF/serum anti-HTLV-I antibody ratio indicated intrathecal HTLV-I antibody synthesis. Western blot for HTLV-I and polymerase chain reaction with primers selected for the HTLV-I pol gene were positive in both peripheral blood and cerebrospinal fluid. HTLV-I antigen was also demonstrated after in vitro co-cultivation of mononuclear cells from peripheral blood. Thus, our findings indicate that HTLV-I infection also may be associated with dementia. In addition, this case report calls attention upon HTLV-I as a possible etiologic agent to neurological diseases in countries previously spared from the infection.

Blotting, Western↗

Identification of the gastrointestinal absorption site for cadmium chloride in vivo.

Most models for the study of the mechanism of intestinal absorption of Cadmium (Cd) have been using intestinal tissue in vitro or in situ. The in vivo experiments reported in this article were performed in an attempt to localize the site for gastrointestinal absorption of cadmium chloride during natural physiological conditions by oral exposure of mice to 109Cd-labelled CdCl2. Independent of exposure via drinking water or oral administration of a single dose, Cd was primarily deposited in the most proximal duodenum. Thus the present study as well as others indicate that absorption takes place in the proximal part of the intestine. Absorbed Cd is initially transported to the liver and deposited before being redistributed and accumulated in the kidneys. In this experimental model, dietary tetraethylthiuram disulfide exposure was shown to change the intestinal labelling profile and increase the whole-body retention as well as the intestinal deposition of Cd.

Administration, Oral↗

Effects of dietary alpha-tocopherol and beta-carotene on lipid peroxidation induced by methyl mercuric chloride in mice.

Exposure of male CBA mice to methyl mercuric chloride, CH3HgCl, (10-40 mg/l in drinking water) for 2 weeks resulted in dose-related Hg deposition and enhanced lipid peroxidation in liver, kidney and brain. Mice were fed well-defined semisynthetic diets containing different levels of alpha-tocopherol (10, 100 or 1000 mg/kg) or beta-carotene (1000, 10,000 or 100,000 IU/kg) for four weeks, two groups on each diet. The concentrations of alpha-tocopherol and beta-carotene used corresponded to deficient, normal and high levels. During the last two weeks, one group on each diet was given 40 mg CH3HgCl/l of drinking water. High dietary alpha-tocopherol protected against CH3HgCl induced hepatic lipid peroxidation, whereas the alpha-tocopherol deficient diet further enhanced CH3HgCl induced hepatic lipid peroxidation. Similar, though statistically non-significant effects occurred in the kidneys, alpha-Tocopherol did not protect against CH3HgCl induced lipid peroxidation in the brain. Excess dietary beta-carotene further enhanced CH3HgCl induced lipid peroxidation in liver, kidney and brain. CH3HgCl significantly decreased the activity of total glutathione peroxidase (T-GSH-Px) and Se-dependent glutathione peroxidase (Se-GSH-Px) in the kidneys in all dietary groups. High dietary alpha-tocopherol enhanced the activity of Se-GSH-Px in liver and kidney compared to the activity in mice fed the normal level of alpha-tocopherol. This occurred in mice exposed to CH3-HgCl as well as in unexposed mice, and the difference between CH3HgCl exposed and unexposed mice was not diminished. High dietary alpha-tocopherol increased the activity of both Se-GSH-Px and T-GSH-Px in the brain of CH3HgCl-exposed mice. The dietary level of beta-carotene did not affect the activity of the two enzymes in the organs investigated.

Animals↗

Regional cerebral blood flow in multiple sclerosis measured by single photon emission tomography with technetium-99m hexamethylpropyleneamine oxime.

The regional cerebral blood flow (rCBF) in 19 patients with multiple sclerosis (MS), 10 with a relapsing remitting course and 9 with a progressive course, was examined by single photon emission computed tomography (SPECT) using technetium-99m hexamethylpropyleneamine oxime ([99mTc]-d,l-HM-PAO) as flow tracer. Nine age-matched volunteers served as controls. Low rCBF in the frontal grey matter correlated with neurological disability (p < 0.01), low frontal grey and white matter perfusion correlated with impaired cognitive functions (p < 0.02), and low rCBF in the occipital regions correlated with impaired visual functions (p < 0.03) in the MS population. A relationship was also found between reduced parietal white matter perfusion and the duration of the disease (p < 0.005). Patients with progressive MS had significantly reduced rCBF in the frontal grey matter compared with relapsing remitting MS patients and controls (p < 0.05). No other rCBF differences were found. As a diagnostic tool in MS, SPECT-[99mTc]-d,l-HM-PAO was found to be insensitive.

Adult↗

Physical training effects in myasthenia gravis.

Eleven patients with mild or moderate myasthenia gravis (MG) were subjected to a strength training program of 27 to 30 sessions during ten weeks. Voluntary maximal muscle force and the degree of fatigue during repetitive maximal isometric muscle contractions were measured in three muscle groups. The subjects did not experience any subjective discomfort or any adverse effect on their MG due to the training. A 23% increase of the maximal voluntary muscle force in knee extension in the trained side was found, compared to 4% in the untrained side (p < 0.05). Only small changes were noted regarding maximal muscle force in elbow flexion and extension or in any of the muscle groups in the fatigue test. Physical training can be carried out safely in mild MG and provides some improvement of muscle force.

Adult↗

Calcium-dependent and calcium-independent signals in the conglutinin-binding assay (KgBa) for immune complexes. Influence of anti-collagen-antibodies.

A solid phase ELISA conglutinin-binding assay (KgBa) was evaluated for the detection of circulating immune complexes. ELISA wells were coated with purified bovine conglutinin and incubated with test sera. Bound IgG was detected with enzyme labelled anti-immunoglobulin. Heat aggregated IgG which had been "solubilized" (i.e., complement treated by incubation with serum) was employed as a reference. The binding of the complement-reacted IgG to solid phase conglutinin was found to be calcium-dependent and inhibitable with N-acetyl-D-glucosamine (GlcNAc). Prolonged incubation (4 days) of aggregated IgG with serum at 37 degrees C abolished the binding to conglutinin, a finding consistent with the complete degradation of deposited C3b to C3c and C3d. The solubilized IgG that bound to solid phase conglutinin was found by gel chromatography to be of high molecular weight (greater than 600 kDa). Binding of IgG to solid phase bovine conglutinin was also observed to a variable degree in normal and pathological sera. However, in this situation the IgG binding was largely calcium-independent, was not inhibited by GlcNAc and did not decrease after prolonged incubation of the serum at 37 degrees C. The reactive IgG eluted on gel chromatography at the position of monomeric IgG suggesting binding via the antigen binding sites. Binding of this IgG was inhibited by both collagen type II and purified conglutinin. These observations suggest that the assay detects cross-reacting autoantibodies against collagen epitopes, or, alternatively, antibodies against the dietary antigen, bovine conglutinin.

Acetylgalactosamine↗