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Biomedical subjects

I Lorenzen

Publications and source records attributed to I Lorenzen.

At least 91 records · Page 5Linked to original sources
PubMed1985

Prognosis in glomerulonephritis. A follow-up study of 395 consecutive, biopsy-verified cases. I. Classification, renal histology and outcome. Report from a Copenhagen study group of renal diseases.

Between 1967 and 1977, 395 consecutive cases of glomerulonephritis (GN) were collected by a Copenhagen study group. The diagnosis was established by histological and biochemical criteria. Light microscopy investigations of thin silver-stained sections were applied. In a follow-up in 1980 all cases were categorized by one of the following end points: death without uremia, uremia, recovery, or censored cases. The course is presented in figures showing the cumulated distribution of outcomes in relation to observation time. Each histological subgroup of GN had its own characteristic course with respect to initial rates of changes in the renal state, as well as to frequency of recovery, uremia and death. The prognosis was good in minimal changes GN and proliferative GN, bad in unclassified GN and worst in extracapillary GN. When part of a connective tissue disease, GN carried a poor prognosis. We conclude that histological classification of GN based on light microscopy offers a reliable means of predicting the long-term prognosis.

Adolescent↗
PubMed1985

Vascular injury compared to ageing of normal rabbit aorta. Biochemical and histochemical studies on time-dependent alterations of vascular connective tissue.

Male albino rabbits of the Danish country strain, 5 months of age, were divided into two groups. One group of animals was killed 180 days after a single mechanical dilatation injury of the thoracic aorta. A second group of untreated controls was killed at ages of 150, 165, 180, 210, 330, and 450 days. Glycosaminoglycans, uptake of 35S-sulphate, collagen, uptake of 125I-albumin, and vascular histochemistry and morphology were analyzed in the thoracic aorta. In the injured aortae the dry weight and the total amounts of hexosamine, hyaluronic acid, chondroitin-4,6-sulphate, dermatan sulphate, heparan sulphate, and hydroxyproline were increased. The concentration of hyaluronic acid decreased, whereas the concentration of dermatan sulphate increased. The concentrations of chondroitin-4,6-sulphate and heparan sulphate were unchanged. The total uptake of 35S-sulphate into the sulphated proteoglycans as well as the uptake of 125I-albumin were increased. The light microscopical examination showed thickening of the intima, medial changes with fibrosis, accumulations of proteoglycans, calcifications, formation of cartilage, and ossified tissue with haematopoiesis. In the uninjured thoracic aorta the only significant change during ageing was an increase in the total amount of hyaluronic acid and a decrease of the 35S-sulphate incorporation into the chondroitin-4,6-sulphate in the aorta. No morphological or histochemical alterations were observed during ageing. Spontaneous lesions were observed in 2 out of 55 aortas. It may be concluded that injury and ageing are reflected quite differently in the thoracic aorta of the rabbits. The observations may be of relevance to the interpretation of the alterations in human arterial diseases involving processes of injury and repair as well as ageing.

Aging↗
PubMed1984

Effect of D-penicillamine on the mechanical properties of aorta, muscle tendon and skin in rats.

The biomechanical properties of rat aorta, muscle tendon and skin were studied after daily D-penicillamine treatment (500 mg/kg) for 5, 10 and 42 days. D-Penicillamine treatment for 5 days resulted in increased aortic extensibility. After long-term treatment the aorta exhibited a shift towards decreased extensibility and increased stiffness at small 'stress' values. Simultaneously the dry weight and diameter of the aortic samples were increased after D-penicillamine treatment for 42 days. After correction of the mechanical parameters for the increased amount of tissue of the samples, the stiffness at small 'stress' values was still increased and the mechanical stability at high 'stress' values retained. This is in contrast to the marked reduction in the strength of muscle tendon and skin of the same animals after D-penicillamine treatment for 42 days. This study demonstrates that a primary increase in the extensibility of aorta may elicit a reactive formation of vascular connective tissue. It is proposed that aortic smooth muscle cells are activated by an increased pulsatile distension of the vessel wall secondary to the early effect of D-penicillamine on collagen and elastin. The resulting excess deposition of collagen and elastin leads to increased stiffness, which may in turn increase the susceptibility of the aortic wall to hemodynamic injury. Consequently D-penicillamine may not as proposed counteract the development of atherosclerosis.

Animals↗
PubMed1984

T lymphocyte subsets in homosexual men from Copenhagen.

Screening of sixty-six asymptomatic homosexual men from Copenhagen revealed significantly lower Leu-3a/Leu-2a ratios as compared to controls. Ten (15%) of the homosexuals had a ratio less than or equal to 1.0. The low Leu-3a/Leu-2a ratios were the result of an increase in the absolute number of Leu-2a cells. Homosexuals with many partners and those who had been sexual partners of patients with the acquired immuno-deficiency syndrome (AIDS) had significantly lower ratios than those without these features. Cytomegalovirus was isolated from urine and/or sputum of 15% and this was associated with a Leu-3a/Leu-2a ratio less than or equal to 1.0. The observed immunological abnormalities could either represent latent infection with the putative AIDS agent or alternatively be caused by repeated infections and/or exposure to allogenic spermatocytes or lymphocytes.

Acquired Immunodeficiency Syndrome↗
PubMed1984

The prognosis of asymptomatic homosexual men with decreased T-helper to T-suppressor ratio.

Screening of 70 asymptomatic homosexual men in Copenhagen revealed that 13 (19%) had T-helper to T-suppressor (H/S) ratios less than or equal to 1.0. Clinical and immunological follow-up examinations for 2-7 months (mean, 5.2 months) disclosed that none of the 13 men developed the acquired immunodeficiency syndrome (AIDS) or AIDS-like symptoms. An increase in H/S ratios to greater than 1.0 was observed in 11 of the 13 men during the time of observation. The decreased H/S ratios were due to an increase in the T-suppressor population. The T-helper population did not at any time differ from that found in 31 male control subjects. The biological relevance of the observed decrease in H/S ratios was supported by the demonstration of a positive correlation to a decrease in the proliferative response of the lymphocytes. Serological studies did not reveal any specific infectious background for the low H/S ratio found in the 13 men, and the reason for the 'spontaneous' increase during the time of observation remains unknown. The present results indicate that most asymptomatic homosexual men with a decreased H/S ratio will experience normalization of the immunological variables.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Effect of D-penicillamine pre- and post-implantation treatment on formation of sponge-induced granulation tissue in rats.

DNA, collagen and sulfated glycosaminoglycans (GAGs) of rat sponge granulation tissue were studied after 42 days of D-penicillamine (D-pen) treatment at 100, 250 or 500 mg/kg/day, starting 10 days before or 28 days after induction of granulation tissue formation. The effects were compared with those observed when the same dosage was started at the onset of the granulation tissue formation and with pair-fed controls. D-pen stimulated the cell invasion into the sponge implants, as manifested by an increased DNA content, particularly with pre-treatment. Pre-treatment reduced the net deposition of of collagen per cell as assessed by the lower hydroxyproline/DNA ratio, at the lower dose leading to reduced collagen concentration. The total amount of granulation tissue collagen remained essentially unaffected within the observation period. Salt-soluble collagen was augmented in a dose-dependent manner, irrespective of treatment protocol, signifying decreased collagen cross-linking. Both pre- and post-implantation treatment enhanced the radiosulfate incorporation into sulfated GAGs, regardless of dose, whereas treatment from the day of sponge implantation had no effect. It is concluded that D-pen enhances the early connective tissue response to injury. Reduction of collagen cross-linking and net collagen deposition, concomitant with stimulation of the proteoglycan metabolism, may pertain to the antirheumatoid activity of D-pen. The observations suggest that long-term administration of D-pen, starting before new attacks of arthritis, may be most effective in controlling developing articular fibrosis.

Animals↗
PubMed1984

The renal excretion of prostaglandins and changes in plasma renin during treatment with either sulindac or naproxen in patients with rheumatoid arthritis and thiazide treated heart failure.

Ten patients with rheumatoid arthritis (RA) and concomitant heart failure were treated with either naproxen or sulindac in an open randomized study to study the drugs' effects on the urinary excretion of prostaglandins on the plasma renin level and on the renal function of the group. Both drugs were given for 14 days and caused a similar and marked decrease in renal excretion of the prostaglandins PGE2 and PGF2 alpha and in plasma renin in all patients. There was no significant effect on the diastolic blood pressure, the body weight or the 24-h creatinine clearance and the clinical effect on the joint symptoms was identical. We conclude that both sulindac and naproxen inhibit the renal prostaglandin synthesis in patients with RA.

Adult↗
PubMed1983

Reversibility of D-penicillamine induced collagen alterations in rat skin and granulation tissue.

Granulation tissue was produced in rats by subcutaneous implantation of Visella sponges. D-penicillamine (D-pen) 100 or 500 mg/kg was administered daily for 42 days by gastric tubing. Pairfed, placebo treated animals were included as controls. Half of the groups were kept for additionally 28 days without medication. The inhibitory effect of D-pen on cross-link formation in newly synthesized collagen was readily reversible. By contrast, cross-link deficiency lasting beyond the observation period was observed in the higher polymeric collagen variants released by dilute acid, heat exposure or limited pepsin proteolysis as estimated by solubility, alpha/beta chain ratio and/or aldehyde content. By SDS-polyacrylamide gel electrophoresis on gels containing 3.6 M urea it was shown that purified dermal acid soluble collagen from treated animals consisted of a mixture of type I and III collagen, whereas only type I collagen was detected in controls. The band pattern was identical in reduced and unreduced collagen samples. Four weeks after D-pen discontinuance type III collagen had disappeared from the acid extract. Moreover, the ratio of type III to type I collagen in the pepsin digest from both granulation tissue and skin showed a persistent rise with D-pen. These observations indicate that D-pen destabilized type III collagen in particular by interference with its disulfide linkages. The amount of granulation tissue remained unaffected throughout the experiment, whereas the skin collagen content decreased at the higher dose level. The regeneration was not completed by the end of the observation period. Modulation of the molecular stability of granuloma collagens may be of relevance for the antirheumatoid effect of D-pen, but the sustained effect on normal tissues may imply a long standing impairment of their supportive capacity.

Animals↗
PubMed1983

Circulating immune complexes in rheumatoid arthritis with extra-articular manifestations.

Circulating immune complexes (CIC) and complement C4, C3 and CH50 levels in serum were monitored during 6-30 months in 10 patients with rheumatoid arthritis and extra-articular manifestations (EM). A total of 58 observations were made, 17 at times when new EM emerged, 41 at times when the patients were in a steady state. CIC were demonstrated by two methods, viz. a complement consumption test (CCT) and a polyethyleneglycol (PEG) precipitation assay. The precipitates were analysed for their content of IgG, IgM and IgA. The CCT titre decreased significantly at the time of a new EM, whereas PEG precipitates were found most often at this time. Two types of precipitate could be demonstrated. One consisted of IgG only, which was found most often when the patients were in a steady state. The other one was composed of IgG and other immunoglobulins, most often IgA. The latter type was found most often at the time when the patients developed new EM. Subnormal serum complement levels were demonstrated frequently. The level of C4 was significantly lower at the time of a new EM, compared with the level of patients with RA but without EM. The decrease in anticomplementary effect and the signs of complement activation suggest that the qualitative and quantitative changes in CIC observed at the time of new EM were the cause rather than the consequence of the clinical manifestations.

Aged↗
PubMed1983

Clinical synovitis and radiological lesions in rheumatoid arthritis. A prospective study of 25 patients during treatment with remission-inducing drugs.

The joints of hands and feet of 25 patients (1150 joints) with rheumatoid arthritis were compared, joint by joint, clinically and radiologically, over 2 years of treatment with remission-inducing drugs. Joints with clinical signs of synovitis decreased from 47% to 17% (p less than 0.001), while the number of joints with radiological lesions increased from 23% to 27% (p less than 0.01). Definite radiological progression of bone lesions was seen in 7% of the joints. Joints with clinical synovitis had a higher risk of progressive bone damage than joints without clinical synovitis (p less than 0.001) and joints in which the clinical signs of synovitis persisted during the study had a higher risk of progressing bone lesions than joints in which the clinical synovitis subsided (p less than 0.001). Progressive bone damage was seen more often in swollen joints than in tender joints without swelling or joints without clinical signs of synovitis (p less than 0.001), the difference in radiological progression between the latter two groups being non-significant. Twenty-one per cent of the joints with progressive bone lesions had no clinical signs of synovitis during the period.

Adult↗
PubMed1983

Serum ferritin and the assessment of iron deficiency in rheumatoid arthritis.

In order to evaluate the diagnostic and pathogenetic importance of s-ferritin and p-lactoferrin in the anemia of rheumatoid arthritis (RA), 38 patients were examined. Twenty-one out of 38 randomly selected anemic patients with classical or definite RA had iron deficiency, as estimated from the iron content in stained bone marrow aspiration. S-ferritin concentrations below 60 micrograms per litre had sensitivity and a specificity for iron deficiency of 86% and 88%, respectively, which was much better than such commonly used variables as s-iron, p-transferrin, MCV, and MCHC. Although this cut-off level is higher than in patients without inflammatory disease, s-ferritin was not correlated to disease activity. In 7 out of 8 patients, the s-ferritin level rose during iron therapy. P-lactoferrin values were within the normal range and did not vary with the anemia or with disease activity. Thus p-lactoferrin appears to be of no pathogenetic importance in the anemia of RA.

Adult↗
PubMed1983

Treatment of rheumatoid arthritis with prostaglandin E1 precursors cis-linoleic acid and gamma-linolenic acid.

20 patients with active rheumatoid arthritis were treated for 12 weeks with the prostaglandin E1 precursors cis-linoleic acid and gamma-linolenic acid in the form of primrose evening oil (Efamol) and the co-factors zinc, ascorbic acid, niacin, and pyridoxin (Efavit). There was a slight fall in skin reactivity to UV light during the treatment, but no effect on plasma or urine concentrations of PGE1, cAMP or cGMP. There was no effect of the treatment on ESR, P-fibrinogen, number of tender joints, number of swollen joints, the duration of morning stiffness, or on the patient's estimation of pain.

Adult↗
PubMed1983

Treatment of severe rheumatoid arthritis.

The basis for the application of remittive agents in rheumatoid arthritis is still hypothetical and empirical. Immunoreactions may be of pathogenetic significance in rheumatoid arthritis but definite evidence is lacking. Similarly the rheumatoid inflammation may be 'non-specific' or immune mediated. Therefore at present there is no basis for 'guidelines' for immunotherapy. Controlled trials have provided little or no information on the mechanism of action of the remittive agents. Furthermore classical controlled trials have severe limitations and require great resources. Therefore we need a new strategy for controlled trials. The emphasis should be on elucidation of the mechanism of actions of remittive agents with already established clinical efficacy. It is now possible in controlled trials to analyse immunological factors of possible pathogenetic significance, factors in the processes of inflammation and the interaction between the immune system, inflammation and connective tissue. Thereby a proper evaluation of the mechanism of action of remittive agents as well as of pathogenetic factors in rheumatoid arthritis seems possible.

Anti-Inflammatory Agents↗
PubMed1983

D-penicillamine-induced angiopathy in rats. The effect of high dose D-penicillamine treatment on aortic permeability to albumin and on the ultrastructure of the vessel.

Male Sprague-Dawley rats were treated with D-penicillamine (D-pen) 500 mg/kg/day for 10 or 42 days. Pair fed rats served as controls. Changes in aortic morphology were examined by light- and transmission-electron microscopy (TEM). In addition, the endothelial permeability and the penetration through the aortic wall of albumin were studied 10 minutes, 24 and 48 hours after i. v. injection of human serum 131I-albumin (131I-HSA). TEM revealed extensive elastolysis in the arterial wall of D-pen-treated rats, consistent with an inhibitory effect on crosslink formation. In experimental animals excess deposition of collagen and glycoaminoglycans was observed in the subendothelial and medial layer of the aortic wall, together with prominent basal membrane substance around aortic smooth muscle cells. The aorta/serum-ratio and the radioactive build-up 24 and 48 hours after injection of 131I-HSA was reduced in animals treated with D-pen for 42 days, indicating an impeded transmural transport of tracer which may be caused by a steric exclusion effect of abundant hyaluronate. The endothelial ultrastructure was unaffected by D-pen, and no differences in aortic 131I-HSA radioactivity or aorta/serum-ratio were recorded between experimental and control groups 10 minutes after tracer injection, indicating that the permeability of the endothelial barrier to albumin remained unaffected by D-pen treatment. These observations support the hypothesis that treatment with high doses of D-pen may induce a fibroproliferative response in rat aorta, possibly by an inhibitory effect on the cross-linking of collagen and elastin.

Animals↗