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Biomedical subjects

O Andersen

Publications and source records attributed to O Andersen.

At least 235 records · Page 13Linked to original sources

Autoimmune haemolytic anaemia treated with multiple transfusions, immunosuppressive therapy, plasma exchange, and desferrioxamine.

Severe autoimmune haemolytic anaemia in a five year old boy was unaffected by treatment with prednisone and splenectomy, but subsided after combined immunosuppressive therapy and three plasma exchanges. Over five months, a total of 93 transfusions of concentrated erythrocytes was given (equal to 18.6 grams of iron or 1.1 g/kg BW). This resulted in severe iron overload with cardiac, hepatic, and pancreatic complications, together with growth-retardation. These complications disappeared after treatment with desferrioxamine and vitamin C, but despite a normal growth hormone response to glucagon the concentration of somatomedin in serum remained low. Treatment by plasma exchanges and immunosuppressive agents may therefore be of value in severe haemolytic anaemia refractory to corticosteroids and splenectomy. Iron chelating therapy should be considered if multiple transfusions result in iron overload.

Anemia, Hemolytic, Autoimmune↗

Chelation of cadmium.

The toxicity of cadmium is determined by chelation reactions: in vivo, Cd2+ exists exclusively in coordination complexes with biological ligands, or with administered chelating agents. The Cd2+ ion has some soft character, but it is not a typical soft ion. It has a high degree of polarizability, and its complexes with soft ligands have predominantly covalent bond characteristics. Cd2+ forms the most stable complexes with soft donor atoms (S much greater than N greater than 0). The coordination stereochemistry of Cd2+ is unusually varied, including coordination numbers from 2 to 8. Even though the Cd2+ ion is a d10 ion, disturbed coordination geometries are often seen. Generally, the stability of complexes increases with the number of coordination groups contributed by the ligand; consequently, complexes of Cd2+ with polydentate ligands containing SH groups are very stable. Cd2+ in metallothionein (MT) is coordinated with 4 thiolate groups, and the log stability constant is estimated to 25.5. Complexes between Cd2+ and low molecular weight monodentate or bidentate ligands, e.g., free amino acids (LMW-Cd), seem to exist very briefly, and Cd2+ is rapidly bound to high molecular weight proteins, mainly serum albumin. These complexes (HMW-Cd) are rapidly scavenged from blood, mainly by the liver, and Cd2+ is redistributed to MT. After about 1 day the Cd-MT complex (MT-Cd) almost exclusively accounts for the total retained dose of Cd2+, independent of the route of exposure. MT-Cd is slowly transferred to and accumulated in kidney cortex. The acute toxicity and interorgan distribution of parenterally administered Cd2+ are strongly influenced by preceding MT induction, or decreased capacity for MT synthesis; however, the gastrointestinal (GI) uptake of Cd2+ seems unaffected by preceding MT induction resulting in considerable capacity for Cd2+ chelation in intestinal mucosa, and this finding indicates that endogenous MT is not involved in Cd2+ absorption. The toxicity of parenterally administered Cd2+ is strongly enhanced when administered as complexes with NTA or STPP , but it is much decreased when administered as a complex with EDTA. In chronic oral exposure the toxicity and GI uptake of Cd2+ is not changed when Cd2+ is administered as a complex with the detergent formula chelating agents NTA, EDTA and STPP . The uptake of Cd2+ from ligated intestine in vivo was not affected by administration of Cd2+ as complexes with CYS or GSH, but significantly reduced by complexation with EDTA or BAL. The acute toxicity of orally administered Cd2+ is reduced when Cd2+ is administered as a complex with EDTA.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Hereditary diffuse leucoencephalopathy with spheroids.

The clinical, genetic, and morphological features of a previously unknown progressive neuropsychiatric disease are presented. By genealogical investigation of the background of an uncharacteristic case of presumed organic psychosis, we traced 71 relatives from four generations. The anamnestic data showed various combinations of psychiatric symptoms (depression, anxiety, aggressiveness, and severe dementia), neurological symptoms (impaired balance with retropulsion, hyperkinesia, and epilepsy), and somatic symptoms (gastrointestinal disorders, arthritis, and gynaecological problems) in 17 (11 dead and 6 living) members of the family. Age at onset varied between 8 and 60 years. Some patients rapidly developed severe dementia and died a few months after the onset of symptoms, while in others the course was prolonged with dementia over several decades. The genetic interpretation indicated an autosomal dominant inheritance with possible full penetrance but widely variable expressivity. Morphological studies were performed on the central nervous system of four decreased family members (three siblings and their maternal uncle). The same type of widespread leucoencephalopathy was seen in the four autopsy cases. It was characterised by degeneration and loss of myelin sheaths and axons, occurrence of numerous neuroaxonal spheroids in the affected white matter, accumulation of lipid-laden macrophages, and gliosis. The bilateral, frontal, fronto-parietal, and temporal locations of the most pronounced, diffusely demarcated lesions corresponded fairly well to the symptoms of an organic psychosyndrome with its main substrate in the forebrain. For this new clinico-pathological entity, the name "hereditary diffuse leucoencephalopathy with spheroids" (HDLS) is proposed. As a working hypothesis, it is suggested that not only genetic, but also immunological and possible endocrine factors may contribute to the development of the disease.

Adolescent↗

Absorption kinetics and steady-state plasma concentrations of theophylline following therapeutic doses of two sustained-release preparations.

Ten healthy volunteers received two sustained-release preparations as a single and multiple dose regimen in an open crossover study. Plasma theophylline concentrations were measured by an enzyme immunoassay. The limited fluctuation of the theophylline levels at steady state, with twice daily administration, clearly demonstrated the marked sustained release properties of both preparations. Results indicate similar properties for the two preparations. Significant correlations between the single dose period and steady state were found for Cmax and AUC (r = 0.76 and 0.87, respectively) with one formulation, whereas this was not the case for the other (r = 0.27 and 0.49). The daily dose necessary to keep the plasma concentration within the therapeutic range of 55-110 mumole/liter varied from 7.9 to 22.9 mg/kg. Only mild side effects were recorded, but they were not correlated to the plasma theophylline concentration.

Absorption↗

Interstitial deletion in the "critical region" of the long arm of the X chromosome in a mentally retarded boy and his normal mother.

A family in which an intestitial deletion of the X chromosome, del(X)(q13q21.3), is segregating was ascertained through a boy with cleft lip and palate, agenesis of the corpus callosum, and severe mental retardation. The possible causal relationship to his chromosome abnormality is discussed. Although the deletion occurred within the critical region, the mother showed no signs of gonadal dysgenesis. A phenotypically normal daughter was, as her mother, monosomic for this region of the X, and both showed random inactivation of the X chromosome.

Abnormalities, Multiple↗

The short-term effects of a low-dose oral contraceptive on glucose metabolism, plasma lipids and blood clotting factors.

Twelve young women were prospectively evaluated for the short-term metabolic effects of a low-dose oral contraceptive containing 30 micrograms ethinyl estradiol and 150 micrograms levonorgestrel. To each volunteer a 50 g glucose challenge was administered monthly as a screening test for changes in the glucose metabolism. Fasting and 30 minutes glucose and insulin values were measured and blood specimens were collected for determination of fasting triglycerides, cholesterol and blood clotting factors II, VII, X. During treatment the fasting plasma glucose level decreased significantly in the first two cycles and then normalized. No change in incremental glucose values was observed. Fasting insulin concentrations, incremental insulin values and the insulinogenic index did not change during the study period. Total plasma cholesterol values decreased during treatment, whereas the plasma triglyceride levels were unaffected. Immediately after tablet intake, an increase was found in the blood clotting factors and the elevated levels continued constantly throughout the study period. Comparing the data from the present study with data from previous investigations on low-dose ethinyl estradiol/levonorgestrel compounds, there seems to be no difference in the influence on blood clotting factors, glucose and lipid metabolism between treatment for 3 and 6 months. From the study, it is concluded that the impact of oral contraceptives on metabolic functions may emerge during the initial treatment cycles.

Adult↗

The renin-aldosterone system in nephrogenic diabetes insipidus and the influence of hydrochlorothiazide and indomethacin.

Three generations of a family with nephrogenic diabetes insipidus were studied. Treatment of a male infant patient with hydrochlorothiazide normalized the serum sodium concentration and improved the clinical condition, but did not influence the polyuria. Although indomethacin alone was without long-term effect, combined therapy with hydrochlorothiazide and indomethacin regulated serum sodium better than hydrochlorothiazide alone. The renin-aldosterone system was not activated in healthy carriers or patients with nephrogenic diabetes insipidus neither in infancy during severe hypernatremic dehydration nor in adult patients.

Adolescent↗

Effects of coal combustion products and metal compounds on sister chromatid exchange (SCE) in a macrophagelike cell line.

Investigations of genotoxic effects of particles have almost exclusively been performed by organic extraction, while direct investigations in cells capable of engulfing particles have only been performed in few cases. Thus, in most studies, the eventual effects of particle-associated metal compounds have remained undiscovered. The present study attempted direct measurement of genotoxic effects of particulate coal combustion products by using the P388D(1) macrophage cell line. The capability of these cells for phagocytosis was demonstrated with insoluble particles. The sister chromatid exchange (SCE) test was used for measuring genotoxic effects of test compounds. Dimethylnitrosamine and benzo(a)pyrene did not increase SCE, indicating that the P388D(1) cell line has lost the capacity for metabolism of latent organic carcinogens, reducing the value of these cells for evaluating genotoxic effects of complex particles. Indirect evidence has been obtained that the cell line may be infected with a virus. Thus, interactions between virus and test compound may lead to erroneous results. This should be kept in mind during evaluation of the results. The effects of metals with reported carcinogenic or mutagenic effects on SCE were compared in P388D(1) cells and human lymphocytes: NaAsO(2), CdCl(2), K(2)Cr(2)O(7), CoCl(2), CH(3)HgCl and MnSO(4) increased SCE in both cell systems. Pb(CH(3)COO)(2), BeSO(4) and NiSO(4) had a weak effect on SCE in P388D(1). Pb(CH(3)COO)(2) and NiSO(4), but not BeSO(4), increased SCE in human lymphocytes. Cr(CH(3)COO)(3) increased SCE in human lymphocytes at high concentration, but was a strong inducer of increased SCE in P388D(1) cells, which take up Cr(III) by phagocytosis. This suggests that the Cr(III) ion is an ultimate carcinogenic form of chromium. Generally P388D(1) cells and human lymphocytes respond to in vitro exposure to metals in agreement with reported mutagenic/carcinogenic effects of the metals. Of four precipitated coal fly ash samples tested, only one sample (from an electrostatic precipitator downstream of a cyclone at an electricity generating plant burning pulverized coal) had a clear increasing effect on SCE in P388D(1). Extraction of this sample with medium with 10% serum yielded an extract capable of increasing SCE. The extracted particles still increased SCE, but less than unextracted particles. Emission samples taken with impactor sampler after a dilution probe using controlled cooling of the flue gas were obtained from an oil-fired (one sample) and a coal-fired (one sample < 3 mum and one sample < 3 mum) steam boiler. The only sample increasing SCE was the sample < 3 mum from the coal-fired boiler. Extract from this sample also increased SCE. The results demonstrated that the use of phagocytizing cells for assessment of genotoxic effects of particles offers a useful system, since the particles can be investigated directly. Furthermore, particles, extracted particles and extract can be investigated in the same system.

Air Pollutants↗

Thallium poisoning--toxin elimination and therapy in three cases.

Three cases of thallium poisoning occurred within the same family after eating a meal of poisoned sour milk. The 58 year old mother died after four days cardiovascular insufficiency. Massive thallium concentrations were found in blood, urine, liver and kidney. The 59 year old father presented after four days with a neurology typical for classic thallotoxicosis with potentially lethal blood thallium levels. This patient recovered after therapy including Prussian Blue, forced diuresis and two six hour hemoperfusions with a charcoal column. Urinary elimination of thallium over two weeks was almost 300 mg, whereas a maximum total of 63 mg were removed with hemoperfusion. A retrospective estimate of the total dose ingested and the large distribution volume of thallium suggest that hemoperfusion did not affect the course of the intoxication. The 28 year old son, later convicted for homicide, was admitted on the tenth day after the meal with very discrete neurological symptoms. This patient had low blood and urine thallium levels. He recovered uneventfully after treatment with Prussian Blue and forced diuresis. However, both surviving patients developed alopecia after two weeks. All three patients had raised liver transaminases. Intensive therapy with gut decontamination, Prussian Blue and forced diuresis should be the mainstay of therapy.

Adult↗