Biomedical subjects
Publications and source records attributed to G Asboe-Hansen.
Differentiation of the pemphigus group of diseases from other bullous dermatoses can be established by spreading of blisters by gentle finger pressure. In combination with histopathology, the same test is diagnostic for every single pemphigus disease.
Increased serum values of aminoterminal type III procollagen peptide and hyaluronan (hyaluronate) and enhanced urinary content of hydroxyproline and hydroxylsine containing polypeptides were demonstrated in patients with progressive systemic sclerosis (PSS). The serum propeptide level and the relative urinary excretion of hydroxyproline as polypeptides were related to the extent of cutaneous involvement. Elevated serum propeptide and hyaluronan values were seen in patients who progressed within the following 6 months. Patients with CREST syndrome had normal propeptide values. Reduced renal propeptide clearance is a likely cause of high serum levels of propeptide degradation products demonstrated in PSS. Serum propeptide seems to be a useful novel marker for disease activity and progression in PSS because of its linkage to the actual connective tissue metabolism.
After a review of some pathogenetic and pathologic aspects of scleroderma, the experimental effects of a group of agents that can inhibit the formation of connective tissue, especially the biosynthesis of collagen, are mentioned. These substances were transferred to clinical therapy of scleroderma. Regular determinations of disease activity and guidance of therapy with quantitative and semiquantitative physical and biochemical technics are of utmost importance because treatment without guidance allows for no disclosure of therapeutic failure or recurrence of the disease in due time for readjustment of the treatment.
The bioavailability of D-penicillamine was measured in 24 patients with generalized scleroderma (Progressive Systemic Sclerosis, PSS). Esophageal changes characteristic of generalized scleroderma were present in 15 of the patients, and 3 of those patients had duodenal involvements as well. The plasma concentrations of D-penicillamine were measured at 0 h, 1 h, 2 h, and 4 h after an oral dose of 300 mg D-penicillamine. Patients with duodenal and/or esophageal changes specific for scleroderma had significantly lower bioavailability of D-penicillamine than scleroderma patients without gastrointestinal manifestations. The decreased plasma D-penicillamine in scleroderma patients with involvement of the gastrointestinal tract may be due to an increased degradation of D-penicillamine in the gastrointestinal tract and/or an impaired absorption of the drug. Since the plasma level of D-penicillamine is so sensitive to pathological changes of the gastrointestinal tract, it may be advisable to adjust the dose of D-penicillamine on the basis of measurements of the plasma concentration of D-penicillamine.
D-penicillamine pharmacokinetics were studied in a patient with gastrointestinal progressive systemic sclerosis possibly complicated by malabsorption. D-penicillamine bioavailability was examined after oral, duodenal, intravenous and rectal administration. No D-penicillamine was detectable in plasma after administration to the gastrointestinal tract. The pharmacokinetics after intravenous administration agreed closely with the corresponding situation in healthy volunteers.
Filamentous aggregates of collagen are distinct structures in the pathological dermis. These aggregates are distinguishable from fibrous long-spacing collagen (in vitro and at biopsy) and the Luse body. The aggregates are produced from dermal collagen fibrils by clostridial collagenase and culture-medium extract, which supposedly contains cellular collagenase at a neutral pH, as well as by organ cultures. In vitro experiments showed that carrageenan granuloma contains fibrous long-spacing collagen and segment long-spacing collagen. The granuloma also contains the aggregates. The aggregates were found in skin biopsies from syphilitic chancres, acrosclerotic scleroderma, morphea, mycosis fungoides, myeloid leukemia, mastocytosis and malignant melanoma. These findings indicate that the aggregates are products of the in situ degradation of collagen fibrils by some collagenolytic factor. This factor may originate in fibroblast-like cells, reticulum cells, leukemia cells, mast cells and melanoma cells.
Secretion of type IV collagen by keratinocytes was studied by anti-type IV collagen immunoglobulin in pure keratinocyte culture of the human adult. The cultivated keratinocytes secreted type IV collagen into the space between the cell growth and the underlying fixed film of human skin collagen type I. The secreted collagen was accumulated on the cell surface to form junction structures.
Seven patients with prurigo nodularis and one with aphthous stomatitis were given 40-115 g of thalidomide for 1 to 6 years. They all developed a predominantly sensory peripheral neuropathy mainly involving the lower limbs. Five patients had an unpleasant tight feeling around the feet. Nerve conduction studies showed small sensory action potentials from the lower limbs with normal or only mild slowing of sensory conduction velocity indicating an axonal neuropathy. The dermatological disorder improved dramatically in all, but treatment had to be discontinued because of the severe side-effects. Thalidomide, if used, should be given only over a short period because of its neurotoxic effect.
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Skin biopsies from thirteen patients suffering from Ehlers-Danlos syndrome, including 6 of the mitis type, 4 of the benign hypermobile type, one of the X-linked type, one of the ocular type and one of the periodontitis type, were studied by electron microscopy after routine preparation. Collagen fibrils showed a distorted arrangement of bent, curled or twisted fibrils and thread-like material. Similar changes may be seen in the skin of other hereditary disorders of connective tissue. However, abnormal collagen fibrils in normal skin suggests one of eight types of Ehlers-Danlos syndrome. Clinical variants cannot be differentiated on the basis of ultrastructural findings. Elastic fibres were normal without degenerative changes. Perineurium was lacking in dermal nerves of most patients. Fibroblast-like cells showed no cystic cisterna of endoplasmic reticula.
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Clinical evaluation of scleroderma and the urinary excretion of collagen specific amino acids and uronic acid indicate disease activity and have become a guide for treatment. During an experimental search for inhibitors of the synthesis of collagen and ground substance glycosaminoglycans, a few connective-tissue active agents were selected for therapy of scleroderma: D-penicillamine, benzyl-penicillin-diethylamino-ethylester-hydroiodide, L-glutamine, hydralazine, glucocorticoids, dextro-thyroxine, L-dopa, diphenylhydantion, chlorpromazine, and (+) catechine. Treatment for several years was required to bring about an arrest of progression in 89% of the patients, a regression in three-quarters, and subtotal or total recovery in more than 40%. Indications of favorable prognosis are youth, short disease history, a high total dose of agent, and long duration of the treatment.
The skin of a female Egyptian mummy, embalmed 100-300 A.D., was studied by transmission and scanning electron microscopy. After rehydration with cacodylate buffer containing sucrose, the ordinary technique for transmission electron microscopy was performed on skin of the right shoulder. In epidermal cells, mitochondria and their cristae were identified. Between epidermal cells, desmosomes, half the normal size, were found. In the dermis, collagen bundles and elastic fibres were observed. The collagen fibres had a diameter of 67-91 nm, and the band pattern showed 10-12 sub-bands per one period of 55-61 nm length. The elastic fibres had less amorphous substance than normal and a fibrillar beaded pattern. The dermal components of the skin were well preserved in spite of the mummification. Throughout the dermis and the subcutaneous fatty tissue, a number of bacterial spores were found showing a characteristic appearance. Scanning electron microscopy of hairs showed a layer of the preserving material surrounding hairs, and under it a normal cuticle was seen.
The ultrastructure of bacterial spores found in the skin of an Egyptian mummy was studied. The mummy was embalmed during year 100 to 300 of our era. The bacterial spores showed a characteristic appearance with a core, cortex, coat and exosporium. Their survival and species could not be established.
The ultrastructure of C. neoformans was studied in two cases of cutaneous cryptococcosis. Extracellular and intracellular fungi were observed. Their capsules and clear zones were thick and distinct, but their cytoplasmic organelles were not obvious. In macrophages, a few stages of fungal degeneration could be observed. It could not be ascertained whether the changes were caused by anti-fungal drugs or by an influence by host macrophages. The ultrastructure of the yeast cells in vitro appeared to be that of degenerated cells because of a long culture period.