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Biomedical subjects

I Lorenzen

Publications and source records attributed to I Lorenzen.

At least 109 records · Page 6Linked to original sources
PubMed1982

Severe acquired immunodeficiency in European homosexual men.

Four previously healthy Danish homosexual men developed Kaposi's sarcoma or opportunistic infections with fever of unknown origin and lymphadenopathy. One patient died of a Pneumocystis carinii pneumonia. Three patients had defective cell-mediated immunity with absent leucocyte interferon production and decreased proliferative response to mitogens and antigens. T lymphocyte helper subsets and natural killer cell activity were reduced. Unstimulated mononuclear cells produced leucocyte migration inhibitor factor. Two patients were sexual partners and three had never been to the USA, where cases of severe acquired immunodeficiency have been reported. Thus, the syndrome must also be suspected in European homosexual men who present with fever of unknown origin, opportunistic infections, or Kaposi's sarcoma.

Adult↗
PubMed1982

D-penicillamine-induced angiopathy in rats. Changes in aortic collagen, glycosaminoglycans, DNA and RNA in rats treated with D-penicillamine.

Male Sprague-Dawley rats were treated with D-penicillamine (D-pen) in doses of 100, 250 or 500 mg/kg per day for 10, 32, 42 or 70 days. In addition animals were examined 28 days after withdrawal from 42 day's treatment with D-pen at 100 or 500 mg/kg per day. Pair-fed rats served as controls. The changes in aortic collagen, glycosaminoglycans (GAGs), DNA and RNA were studied. D-Pen had a dose- and time-related solubilizing effect on aortic collagen, which regained normal resistance to extraction within 28 days after cessation of the treatment. In contrast, D-pen caused a progressive accumulation of hydroxyproline (Hyp) in the aortic wall during and after treatment, probably mediated by an increased number of matrix synthesizing cells, as judged by augmentation of the DNA content in the presence of unaltered Hyp/DNA and RNA/DNA ratios. The relative amount of type III collagen was increased after 500 mg/kg per day D-pen for 10 and 42 days. High doses of D-pen increased the percentage of water in the aortic wall and reduced the ratio of Hyp to total tissue protein, suggesting an increased content of water-binding substances. This was confirmed by GAG accumulation. Hyaluronic acid (HA) and chondroitin 4,6-sulphate (CHS) were predominant after 32 and 42 days, whereas CHS, heparan sulphate (HS) and dermatan sulphate (DS) prevailed after 70 days of treatment. These observations suggest that processes of repair and regeneration are elicited secondary to the inhibitory effect of D-pen on aortic collagen and elastin crosslinking. Hypertrophy of the vessel wall may imply an increased rigidity, resulting in further increase of the susceptibility to haemodynamic injury.

Animals↗
PubMed1982

The effect of D-penicillamine and methylprednisolone on the morphology of experimental granulation tissue in rats.

The effects of D-penicillamine and methylprednisolone on the formation of granulation tissue was studied in rats with Visella-sponge induced granulation tissue after 42 days of treatment. D-penicillamine in doses of 20 mg-, 100 mg-, 500 mg/kg/day caused no morphological differences compared with the control groups as regards ingrowth of granulation tissue and its content of collagen fibres, inflammatory cells, vessels and glycosaminoglycans. Treatment with methylprednisolone, 0.2 mg-, 2.0 mg-, and 5.0 mg/kg/day caused a dose dependent reduction in the ingrowth of granulation tissue. Methylprednisolone caused a reduction in the number of fibroblasts and collagen fibres, but no differences in the content of glycosaminoglycans could be demonstrated between the treated and the control groups. Granulation tissue produced during combination treatment with D-penicillamine 100 mg and methylprednisolone 2.0 mg/kg/day did not differ from that observed after methylprednisolone treatment alone. Thus, only high doses of methylprednisolone gave rise to an antiinflammatory action in this morphological study on granulation tissue, whereas D-penicillamine had no effect within the present dose interval. The quantitative alterations are in agreement with parallel biochemical analyses. However, the inhibitory effect of D-penicillamine on collagen crosslinking was not associated with light microscopic changes in the ultrastructure of the collagen fibres.

Animals↗
PubMed1981

Effect of different doses of D-penicillamine and combined administration of D-penicillamine and methylprednisolone on collagen, glycosaminoglycans, DNA and RNA of granulation tissue, skin, bone and aorta in rats.

D-penicillamine (D-pen) in doses of 20, 100 and 500 mg/kg/day or D-pen 100 mg/kg/day plus methylprednisolone (MP) 2.0 mg/kg/day was administered daily for 42 days to rats implanted with viscose-cellulose sponges. Operated, pairfed rats served as controls. D-pen increased the DNA content of granulation tissue, but had no effect on the amount of tissue produced. In contrast, high dose D-pen reduced the content of DNA and collagen in skin. A dose related inhibition of collagen crosslink formation occurred in all tissues, particularly in skin, as indicated by increased proportions of extractable collagen with increased alpha/beta chain ratio and aldehyde content. Moreover, low doses of D-pen increased the hydroxyproline/proline ratio of acid soluble skin collagen, presumably due to solubilization of type III collagen as demonstrated by SDS-polyacrylamide gel electrophoresis in the presence of 3.6 M urea. These changes were associated with increased skin fragility and edema plus excess elastin deposition in the aorta after high dose D-pen treatment. Low dose D-pen stimulated the 35S-sulphate uptake into the sulphated glycosaminoglycans (GAGs) of granulation tissue without altering their relative amounts, whereas high dose D-pen reduced the concentration of chondroitin-4/6-sulphate in skin. MP antagonized the solubilizing effect of D-pen on collagen, probably by inhibition of the collagen synthesis. In addition, MP inhibited the cell proliferation and GAG metabolism. Food restriction reduced the DNA content of granulation tissue. The inhibitory effect of D-pen on the formation of granuloma collagen crosslinks in the presence of unaltered rate of collagen biosynthesis may diminish the amount of fibrotic tissue due to increased degradability of crosslink deficient collagen. Simultaneous administration of MP may facilitate this effect by inhibiting the biosynthesis of collagen. However, long-term D-pen treatment seems to increase the susceptibility of normal tissues to mechanical injury.

Animals↗
PubMed1981

Effect of D-penicillamine on collagen, glycosaminoglycans, DNA and RNA of granulation tissue and connective tissue of skin, bone and aorta in rats.

Granulation tissue was produced by subcutaneous implantation of viscose-cellulose sponges on rats. The effect of D-penicillamine 500 mg/kg/day for 10 days on granulation tissue and the connective tissue of skin, bone and aorta was studied ny comparison of treated animals with operated and unoperated controls. In addition, the effect of sponge implantation on intact tissues was studied by comparison between the control groups. The amount of granulation tissue was not affected by D-penicillamine, and the granulomas-DNA content even increased. D-penicillamine increased the amount of salt soluble collagen in all tissues consistent with an inhibition of collagen crosslinking as reflected by increased aldehyde content and alpha/beta chain ratio in soluble skin collagen. Skin appeared to be most sensitive. The content of free hydroxyproline and RNA and the RNA/DNA ratio in skin decreased suggesting a decreased collagen biosynthesis. The hydroxylation of proline and lysine was not affected by the treatment. The water percentage of aorta increased during D-penicillamine treatment, and the 35S-sulphate uptake in the sulphated glycosaminoglycans was stimulated in all tissues, in granulation tissue mainly in the chondroitin-4/6-sulphate fraction. No quantitative glycosaminoglycan changes occurred in granulation tissue. Sponge implantation caused an increase in the amount of salt soluble skin collagen without any change in alpha/beta chain ratio and aldehyde content of purified, soluble collagen. D-penicillamine plus operation reduced the collagen content of aorta. The effects of D-penicillamine on connective tissue compounds may be of importance for its antirheumatic efficacy, but the accompanying effect on normal tissues may imply side effects.

Animals↗
PubMed1981

Pharmacological control of inflammatory connective tissue diseases.

The primary cause of the most common inflammatory rheumatic diseases in unknown. Microbial infection combined with an increased susceptibility due to genetically determined alterations in the immune system is probably of importance. Non-specific processes of inflammation and repair are the immediate causes of the clinical symptoms, and anti-inflammatory therapy is at present the corner stone in the control of these diseases. The highest priority in research should be given to drugs, which in controlled clinical trials have demonstrated ability to cause remission of disease activity. Important examples are D-penicillamine, glucocorticoids and the cytostatic drugs. The effects of these drugs on the metabolism of proteoglycans and collagen in granulation tissue and normal connective tissue may explain some of the beneficial effects, but also some of the side effects. Rational pharmacotherapy in the inflammatory rheumatic diseases may be a combination of anti-inflammatory drugs with immunotherapy and possibly antimicrobial therapy.

Anti-Inflammatory Agents↗
PubMed1980

Proteoglycans, DNA, and RNA in rat granulation tissue, skin, and aorta. Biochemical and histological studies.

Proteoglycans in skin and aorta and nucleic acids in skin were studied in rats with subcutaneous sponge implants and in unoperated rats and compared with the sponge induced granulation tissue during a 42 day period. In rat aorta there was a predominance of the sulphated glycosaminoglycans, in particular heparan sulphate, while in skin there was a predominance of hyaluronic acid and dermatan sulphate. The subcutaneous sponge implantation caused a decrease in the dry weights of skin and aorta but did not influence the concentrations of the measured variables. In aorta the concentrations of chondroitin sulphate and dermatan sulphate decreased with age while in skin there was a slight fall in the concentrations of hyaluronic acid and heparan sulphate with age. The rate of biosynthesis of proteoglycans as estimated from the 35S-sulphate uptake was higher in skin than in aorta. A sequential development was noticed in granulation tissue with an initial high content of hyaluronic acid followed by increasing amounts of chondroitin sulphate and dermatan sulphate in older granulation tissue. The RNA/DNA ratio reached a maximum in 14 day old granulation tissue, but was unchanged in skin throughout the 42 day period. It is concluded that the distribution of proteoglycans and nucleic acids differs from tissue to tissue. This may be of relevance for tissue differences in susceptibility to diseases and to the effects - and side-effects - of drugs. The morphological and biochemical development of sponge induced granulation tissue from rats was similar to other types of granulation tissue during the first 4 weeks.

Age Factors↗
PubMed1979

Seasonal variations in the biophysical properties of rabbit aorta and its susceptibility to arteriosclerosis.

The physiological variations in the mechanical properties of rabbit aortae in relation to the periods of hair shedding were studied. The load-strain curves of the eight proximal thoracic segment in 15 shedding and 15 non-shedding male albino rabbits were analysed. The slope of the curves (tangent of the angle between the linear region of the load-strain curve and the strain axis) was decreased in the shedding animals compared to that of the non-shedding animals and the toe of the load-strain curves was significantly lower towards the x-axis in the shedding animals. The observations indicate a lower stiffness, that is increased elasticity, of the aortae of rabbits during hair shedding. The increased elasticity during hair shedding may explain the previously reported resistance to experimental arteriosclerosis caused by the hemodynamic strain elicited by exposure to systemic hypoxia. A decrease in the aortic content of collagen and of sulfated glycosaminoglycans, and an increase in the content of hyaluronic acid, may be of importance in the alterations of the mechanical properties of rabbit aorta during hair shedding.

Animals↗
PubMed1979

Prednisone effect on microvascular permeability in patients with inflammatory rheumatic diseases.

The transcapillary escape rate of albumin was measured in 27 consecutive patients with inflammatory rheumatic diseases before and after 1 and 7 days of prednisone treatment in doses of 45 mg/day. The transcapillary escape rate decreased from 7.33%/h (range 5.11-9.55) before prednisone treatment to 3.11%/h (0.04-6.18) (p less than 0.05) after 1 day of treatment and 5.80%/h (4.36-7.24) after 7 days of treatment. It is concluded that prednisone inhibits vascular permeability in patients with inflammatory rheumatic diseases.

Adult↗
PubMed1979

Formation of granulation tissue in subcutaneously implanted sponges in rats. A comparison between granulation tissue developed in viscose cellulose sponges (Visella) and in polyvinyl alcohol sponges (Ivalon).

A comparison was made between the granulation tissue formation in two different synthetic sponge types. Visella and Ivalon, of different sizes. The granulation tissue formed in the two sponge types did not differ qualitatively, and had the character of wound tissue and inflammatory tissue in man. The rate of tissue formation in the Visella sponges was faster and the tissue was more homogenous than in the Ivalon sponges. Fourteen-day-old Visella implants of either size contained more granulation tissue than Ivalon sponges, probably owing to the smaller pore size of the former material. This may also account for the more frequent occurrence of giant cells in the Visella implants. In contrast to the Visella sponges, the trabeculae of the Ivalon polymer showed calcification and positive staining properties with histological staining procedures, and deformation was frequent among the Ivalon implants. Thin sponges of either type closed in about 21 days, thick ones after about 42 days of implantation. Calculated per 2 cm3 of implant, thin sponges produced more tissue after 14 days of implantation than thick noes. It is concluded that the Visella sponge type is best suitable for this experimental model of inflammation.

Animals↗
PubMed1978

Reversibility of the effects of cyclophosphamide on collagen: biochemical studies on skin and granulation tissue and determination of thermal stability of tail tendons of rats.

Granulation tissue was produced in rats by subcutaneous implantation of viscose cellulose sponges. Treatment with cyclophosphamide in a dose of 10 mg/kg/day for 14 days caused an increase in acid soluble OH-proline and a decrease in alpha/beta ratio of acid soluble collagen of granulation tissue. Forty-two days of continuous cyclophosphamide treatment caused a decrease in dry weight, in free OH-proline, and in salt soluble OH-proline in granulation tissue. These findings are in accordance with previous observations of a decreased collagen synthesis and an inhibited collagen degradation in granulation tissue after cyclophosphamide treatment. In skin, the only change after cyclophosphamide was a decrease in total content of OH-proline and an increase in alpha/beta ratio of acid soluble collagen after 42 days of treatment. No effect of the subcutaneous sponge implantation was observed on the collagen variables in the skin. In comparison with unstarved controls, a reduction in dry weight and in free OH-proline in granulation tissue, as well as an increase in salt soluble OH-proline in the skin were observed 28 days after a 14-day treatment with cyclophosphamide. These observations indicate a sustained effect of cyclophosphamide on collagen 28 days after cessation of treatment. In addition the thermal stability of rat tail tendons was decreased 28 days after withdrawal of cyclophosphamide to the same extent as after starvation for 42 days and after 42 days of continuous cyclophosphamide treatment. It is concluded that the cyclophosphamide-induced collagen alterations, which may be of importance in the anti-inflammatory action of cyclophosphamide, are only in part reversible, 28 days after cessation of 14 days of cyclophosphamide treatment.

Animals↗
PubMed1978

Effects of different cyclophosphamide treatment schedules on collagen and collagenolytic activity in granulation tissue.

Cyclophosphamide was injected intraperitoneally into rats in doses of 6 or 10 mg/kg/day. The controls had daily intraperitoneal injections of physiological saline. After 14 days of treatment, granulation tissue was produced by subcutaneous implantation of viscose cellulose sponges. The treatment with cyclophosphamide and physiological saline was continued in different sequences for a further one or two 14-day periods. The rats were killed 14 or 28 days after the sponge implantation. Cyclophosphamide caused a decrease in body weight, in the number of leucocytes, in granuloma dry weight and in the granuloma content of free OH-proline while the water percentage increased. Ten mg/kg/day of cyclophosphamide had a more pronounced effect than 6 mg/kg/day. The results are consistent with an inhibitory effect of cyclophosphamide on granuloma formation and on the degradation of collagen. Accordingly, measurements of collagenolytic activity in granulation tissue after culture in vitro suggested an inhibition of collagenolysis after cyclophosphamide treatment. No effect of pretreatment was observed, and the effect of cyclophosphamide was independent of whether cyclophosphamide was given during the early or late phase of granulation tissue production.

Animals↗
PubMed1978

Cytostatic treatment of glomerular diseases. IV. The effect of combined immunosuppressive treatment on serum creatinine and proteinuria evaluated by sequential statistical analysis. Report from a Copenhagen study group of renal diseases.

Sequential statistical testing of the development of the disease in the single patient was used in the assessment of immunosuppressive treatment of renal glomerular diseases. After an initial period of prednisone (P) treatment, this was supplemented first by azathioprine (A) and later in addition by cyclophosphamide (C). The time of transition from one treatment to another was determined by the result of the current statisical testing of the correlation between serum creatinine concentration and proteinuria on the one hand and the time and the varying doses of the drugs on the other. Twenty-nine patients entered the study. Thirteen were withdrawn, eight for technical reasons, three due to side-effects and two on account of renal deterioration and transfer to dialysis treatment. Eight patients were cured, one during P treatment, five during P + A, and two during the combination of P, A and C. Eight patients completed treatment without being cured. In the overall material no statistically significant change in serum creatinine was noted, whereas the proteinuria decreased during P + A and P + A + C. No dose-dependent therapeutic effect of the drugs was demonstrated. In conclusion, this combined treatment with P, A and C did not seem to yield any major therapeutic progress. The technic of sequential statistical testing may be a useful tool in clinical research.

Adolescent↗