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Biomedical subjects

F Melsen

Publications and source records attributed to F Melsen.

At least 19 recordsLinked to original sources

Postmortem findings in three patients treated with intravenous fat emulsions.

Three patients died of intercurrent illness in relation to intravenous nutrition with fat emulsions (20% Intralipid). In two cases, postmortem findings showed milky white, shiny, clotted lumps in the heart, with a fatty acid composition resembling that of fat emulsions. In vitro investigations make it likely that fibrin deposits in hyperlipemic plasma composed the lumps. In two cases, 30- to 50-mu Sudan-positive accumulations were found in the small vessels of the lungs, the cerebrum, and the kidneys.

Aged

Experimental infusion thrombophlebitis. A comparison between glucose and frutcose and 5% and 10% glucose solution.

On the basis of clinical experience it has been claimed that glucose results in a higher incidence of infusion thrombophlebitis than fructose, and that glucose solutions in concentrations higher than 5% are extremely irritant to the venous endothelium. The validity of these two assertions has been investigated by an experimental method based on a quantitative histological study of rabbit-ear veins into which infusions were given under standardized conditions. In two series of experiments, it was shown (1) that fructose solutions caused significantly more inflammatory changes in the veins than did glucose solutions, and (2) that glucose in 10% solutions caused significantly more injury to the veins than 5% solutions, although the difference in the average inflammatory changes was only slight.

Animals

Myopathy in bone loss of ageing: improvement by treatment with 1 alpha-hydroxycholecalciferol and calcium.

1. Eleven patients with the bone loss of ageing were treated with the vitamin D analogue 1 alpha-hydroxycholecalciferol and calcium for 3--6 months. 2. Muscle biopsies were taken from the vastus lateralis before and after the treatment and the activity of several enzymes was measured. Succinate dehydrogenase and total phosphorylase activities, which are a measure of the oxidative capacity, were low and increased significantly with the treatment. The lactate dehydrogenase activity, which can be taken as a measure of the anaerobic metabolism, was normal and did not change with treatment. The phosphagen stores, ATP and creatine phosphate were low and increased to normal with treatment. 3. Histochemical classification of the fibre composition revealed that the treatment induced an increase in the relative number of fast-twitch a (FTa or type II A) fibres accompanied by a reduction of the fast-twitch b (FTb or type II B) fibres. The cross-sectional area of the FTa fibres also increased with the treatment. 4. The present findings indicate that treatment with the active vitamin D analogue, 1 alpha-hydroxycholecalciferol, and calcium improves the myopathy associated with the bone loss of ageing.

Aged

Fractional intestinal calcium absorption in epileptics on anticonvulsant therapy. Short-term effect of 1,25-dihydroxycholecalciferol and 25-hydroxycholecalciferol.

Fractional intestinal 47Ca calcium absorption (alpha) in 12 epileptic outpatients receiving chronic high-dose anticonvulsant therapy was reduced (p less than 0.05) compared to 12 matched normal controls. Six of the epileptics were treated orally with 0.5 microgram of 1,25-dihydroxycholecalciferol (1,25-DHCC) per day and six with 10 microgram of 25-hydroxycholecalciferol (25-HCC) per day for 10 days. The alpha was determined before and after treatment and compared with the effect of 0.5 microgram of 1,25-DHCC per day given for 10 days to 6 controls. An increase of the same order in alpha was found in all groups (p less than 0.05). No changes were observed in the serum levels of calcium, phosphorus, alkaline phosphatase or iPTH during treatment. Urinary calcium excretion was low in the epileptic patients and rose during treatment. The investigation demonstrates that the sensitivity of the intestine to 1,25-DHCC is normal in epileptic patients on anticonvulsant therapy and that 1,25-DHCC and 25-HCC in the given doses had an equal effect on the reduced intestinal calcium absorption.

Administration, Oral

Comparative bone morphometric analysis of mandibles and iliac crests.

A comparative analysis of bone mass in the mandible and the iliac crest has been carried out in autopsy specimens from 30 subjects aged 23-84 years. Microradiograms of standardized 100-micrometer-thick sections of the undemineralized plastic embedded material from the two locations were used for quantitation. The following measurements were carried out by electronic point-counting: 1) the percentage of cortical bone mass in the subperiosteal and subendosteal layers, 2) mean cortical width, and 3) the percentage of trabecular bone mass in the iliac crest. Positive correlations were found in the expressions of bone mass within the mandible; the values were significantly higher in the 200-micrometer-thick subperiosteal layer than in the remaining part of the mandibular cortex. Only a poor or no correlation was found in the expressions of bone mass from the two sites. The investigation, therefore, shows that bone mass and cortical width in the mandible cannot be predicted from a biopsy from the iliac crest. This finding may partly be due to different age-dependent functional changes of the two bones.

Adult

Experimental acute salpingitis in grivet monkeys provoked by Chlamydia trachomatis.

Chlamydia trachomatis is a common cause of sexually transmitted diseases. Recently it has been shown that chlamydiae are also responsible for complications to such lower genital tract infections. In this study, isolates of C. trachomatis from the fallopian tubes of patients with acute salpingitis were inoculated direct into the fallopian tubes of two, and through the cervical canal into the uterine cavity of one grivet monkey. The experimental infections resulted in a self-limited acute salpingitis in the three animals. C. trachomatis was recovered from the monkeys 2 and 3 weeks post inoculation. As found at laparotomy, the infected tubes were swollen and reddened, and there was watery exudate in the abdominal ostia. Microscopically, cellular infiltrates--mainly lymphocytes--were seen in the mucosa, muscularis and subserosa of the tubes. Serologically, a primary antibody response with an IgM to IgG conversion was found. Salpingitis did not occur in a control monkey inoculated in the tubes with a medium lacking Chlamydia. The histological changes in the fallopian tubes of the infected monkeys were reminiscent of those described as being characteristic of "gonococcal" salpingitis in man. The fulfilment of Koch's postulates in the animal model used adds to the earlier evidence that C. trachomatis is capable of causing acute salpingitis in humans.

Acute Disease

Tetracycline double-labeling of iliac trabecular bone in 41 normal adults.

A histomorphometric evaluation of the iliac crest trabecular bone remodeling was performed after tetracycline double-labeling in 41 normal Danes (12 males and 29 females) aged 19 to 56 years. The fraction of formative (osteoid covered) and resorptive surfaces was unrelated to age but higher in males than in females (P less than 0.02 and P less than 0.05, respectively). The appositional rate (0.65 +/- 0.12 micrometer/day) was unrelated to age and sex, whereas the fractional labeled surfaces were higher (P less than 0.01) in the males (0.18 +/- 0.08 micrometer2/micrometer2) than in the females (0.12 +/- 0.05 micrometer2/micrometer2), and among the females inversely related to age (R = -0.38, P less than 0.05). The bone formation rate at BMU level (0.50 +/- 0.20 micrometer3/micrometer2/day) was unrelated to sex, but among the females inversely related to age R = -0.49, P less than 0.01). The bone formation rate at tissue level was higher (P less than 0.02) in the males (0.13 +/- 0.07 micrometer3/micrometer2/day) than in the females (0.07 +/- 0.03 micrometer3/micrometer2/day) and among the females inversely correlated to age (R = -0.43, P less than 0.05). the age- and sex-dependent variations in the dynamic parameters underline the importance of a more elaborated normal material.

Adult

Effects of a single dose of fluoride on calcium metabolism.

Fluoride 27 mg was given perorally to 14 subjects. It was found that the serum fluoride concentration increased followed by a decrease to normal levels during 24 h. Serum concentrations of calcium and phosphate decreased initially whereas those of serum immunoreactive parathyroid hormone increased. After 24 h the measured quantities were within normal limits. The results are discussed with reference to mineralization of hard tissues and to fluoride treatment of osteoporotic patients.

Adult

Do fat emulsions protect against infusion thrombophlebitis? An experimental study.

The clinical experience that a fat emulsion (Intralipid) protects the vein against infusion thrombophlebitis caused by an amino acid solution (Aminosol) was controlled by an experimental method based on a quantitative histological analysis of the inflammatory changes observed in the veins of rabbit ears after infusions. In a controlled blind study, sequential analysis failed to reveal any difference in the histological changes which developed after infusion of Aminosol alone and Aminosol plus Intralipid. In a second series of experiments in which Intralipid was compared with 0.9% NaCl it was demonstrated that the fat emulsion alone gave rise to considerable inflammatory changes in the veins.

Animals

A tetracycline-based histomorphometric evaluation of bone resorption and bone turnover in hyperthyroidism and hyperparathyroidism.

Increased bone, resorption previously found in hyperthyroidism might be caused by a direct stimulating effect of thyroid hormone(s) on bone cells or by an increased sensitivity to circulating parathyroid hormone. In order to disclose qualitative differences in the response of bone resorbing cells to excess parathyroid hormone and excess thyroid hormone(s), histomorphometric analysis of iliac crest biopsies was performed in 25 hyperparathyroid and 40 hyperthyroid patients after tetracycline double-labelling. The main target cells for parathyroid and thyroid hormones were different. Parathyroid hormone stimulated osteocytic osteolysis and increased osteoclastic resorption surfaces equally in trabecular and cortical bone. The osteoclastic resorption was inactive. Thyroid hormone(s) had no effect on osteocytes but increased the osteoclastic resorption surfaces in trabecular and cortical bone, with a pronounced preponderance in cortical bone. The osteoclastic resorption was active and followed by a significant loss of both cortical and trabecular bone. The findings support the assumption that increased bone resorption in hyperthyroidism is caused by a direct stimulating effect of thyroid hormone(s).

Adult

Morphometric and dynamic studies of bone changes in hypothyroidism.

Bone biopsies were performed after tetracycline double-labelling by transfixing the right iliac crest in fourteen hypothyroid patients. The bone changes in cortical and trabecular bone were determined by simple measurement and point counting on decalcified and undecalcified stained sections and compared to normal controls and to sex and age matched hyperthyroid patients. The amount of trabecular bone and the cortical porosity were unchanged in the hypothyroid patients compared to normal controls, whereas the mean cortical thickness was increased. The amount of osteoid and the length of the osteoid seams were normal, whereas the mean width of the osteoid seams was decreased. The linear calcification rate in cancellous bone was decreased, as were the active calcification surfaces (tetracycline-labelled) and the percentage of osteoid covered surfaces active in mineralization. The osteoclastic resorption surfaces were unchanged in trabecular bone, whereas the osteoclastic activity in cortical bone was decreased. The osteocytic osteolysis was normal. The bone changes in hypothyroidism were opposite to the changes in hyperthyroidism characterized by a very low bone turn-over with a reduced osteoid apposition and bone mineralization rate, an inactive osteoclastic resorption in trabecular bone and a decreased osteoclastic resorption in cortical bone.

Adult

An evaluation of the quantitative parameters applied in bone histology.

An evaluation of the following histomorphometric parameters: absolute trabecular bone volume (ATBV), osteoid surfaces (OS), osteoid volume (OV), resorption surfaces (RS), and mean size of periosteocytic lacunae (POL) was carried out. Double determination on sections, obtained from an area 2 cm below the summit and 2 cm behind the anterior, superior, spine of the iliac crest from 20 normal individuals aged 20-40 years, showed that the precision of method by far outweighed the inter-individual variation. Parameters obtained from 9 different localizations within the iliac bone revealed that the volume of bone was the only parameter which was influenced if the bone specimen was removed more than 2 cm below or behind the standard localization. Randomly selected sections alternately stained with Masson trichrome and toluidin blue were used for the study of the influence of the staining method on the osteoid parameters. It was shown that Masson trichrome staining would generally result in a slightly higher value of osteoid surfaces. There was, however, a high correlation between the parameters obtained with the two methods. (OS: r = 0.96; OV: r = 0.87).

Adult

Histomorphometric analysis of normal bone from the iliac crest.

Bone specimens from a standardized area of the iliac crest were obtained at autopsy in 105 individuals after sudden unexpected death and at biopsy in 30 living volunteers. Seven micron thick sections of the plastic embedded undecalcified material were produced and stained. The amount of cancellous and cortical bone and the parameters attached to description of bone remodelling were determined by point counting and simple measurements, in order to establish normal mean values and range in a Danish population. A decrease in the amount of bone, trabecular as well as cortical, was found with increasing age in both males and females. The extent, volume and width of osteoid seams and the osteoclastic resorption were found to be age-independent. The osteoclastic resorption in cortical bone in males decreased, however, with increasing age. The reported values are of the greatest importance for the use of histomorphometric analysis of bone biopsies as a diagnostic tool in metabolic bone diseases. It is stressed, however, that supplementary information of the dynamic aspects of the bone remodelling would be necessary for the understanding of the pathogenesis of bone changes. Such information might be obtained by using tetracyline double labelling.

Adolescent

Effect of antithyroid treatment on calcium-phosphorus metabolism in hyperthyroidism. I: Chemical quantities in serum and urine.

The effect of antithyroid treatment on the disturbed calcium-phosphorus metabolism in hyperthyroidism was studied in 16 patients. Elevated serum concentrations and urinary excretions of calcium and phosphorus were almost normalized 4 weeks after the start of medical treatment. Serum immunoreactive parathyroid hormone was decreased in the hyperthyroid state and became normal after medical treatment. Serum alkaline phosphatase levels were elevated throughout the study with an increase to a maximum peak after 8 weeks of antithyroid treatment. Urinary hydroxyproline excretion was initially markedly increased and fell rapidly during therapy. The observed changes suggest decreased bone resorption and increased bone formation with deposition of bone mineral after antithyroid treatment. Alterations in the serum albumin concentration during the investigation period influenced the total serum calcium concentration. Using albumin adjusted serum calcium values no hypocalcaemia was found during medical treatment or after a subsequent subtotal thyroidectomy.

Adult

Effect of antithyroid treatment on calcium-phosphorus metabolism in hyperthyroidism. II: Bone histomorphometry.

Histomorphometric analysis of iliac crest biopsies was performed after tetracycline double-labelling in 22 hyperthyroid patients before and after medical antithyroid treatment for an average period of 4 months. The initially increased cortical porosity was normalized during treatment whereas the amount of trabecular bone was unchanged. The osteoclastic resorption in cortical bone decreased but was still elevated. The osteocytic osteolysis remained slightly increased. In trabecular bone, however, the bone turn-over decreased to a subnormal level following treatment and the surfaces were inactive in bone resorption and bone formation. An increase was observed in the amount, extent and width of osteoid seams due to an increase in the lifespan of bone forming sites and a prolongation of the maturity period of osteoid. The observed increased deposition of cortical bone after antithyroid treatment may explain the positive calcium balance in this period.

Adult

Bone phosphorus/hydroxyproline ratio and bone histomorphometry in normals.

Bone phosphorus/hydroxyproline ratio (P/Hypro) was compared to bone histomorphometry in thirty-four normal individuals. Bone P/Hypro ratio correlated significantly to both the relative mineralized bone volume (r = 0.38, P less than 0.05), the relative osteoid volume (r = -0.38, P less than 0.05) and the percentage of osteoid covered surfaces in trabecular bone (r = -0.38, P less than 0.05).

Adolescent