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Biomedical subjects

I Lorenzen

Publications and source records attributed to I Lorenzen.

At least 73 records · Page 4Linked to original sources
PubMed1988

Serum aminoterminal type III procollagen peptide. Relation to biosynthesis of collagen type III in experimentally induced granulation tissue in rats.

Serum aminoterminal type III procollagen peptide was measured in rats during the development of granulation tissue induced by subcutaneous implantation of viscose cellulose sponges. Active collagen type III synthesis in granulation tissue during the first three weeks was accompanied by an increase in serum propeptide level. A positive correlation was observed between the increase in serum propeptide level on the one hand and the increase in granulation tissue collagen type III content and the in vitro formation of tissue 3H-hydroxyproline on the other hand. In some animals the serum propeptide level remained low, despite biochemical signs of collagen synthesis, indicating variations in the release into serum and/or the metabolism of circulating propeptide. The increase in propeptide antigen concentration was mainly due to an elevated content of material with molecular weight equal to or twice that of the propeptide. A minor fraction of the propeptide remained attached to the interstitial collagen fibres in the granulation tissue. The correlation between the serum propeptide level and the biosynthesis of collagen at the site of the focal fibroproliferative process suggests that the serum propeptide level may be a valuable indicator of fibrogenesis and thereby of disease activity in fibrotic conditions.

Animals↗
PubMed1988

Cytostatic treatment of glomerular diseases. V. Treatment of glomerulonephritis with cyclophosphamide plus prednisone, azathioprine plus prednisone and cyclophosphamide as monotherapy. A comparative study. A report from a Copenhagen Study Group of Renal Diseases.

Thirty-two patients suffering from biopsy-proven glomerulonephritis with proteinuria greater than or equal to 1.2 g/24 hours and/or creatinine clearance less than 50% of normal value were treated for 6 weeks with prednisone plus cyclophosphamide (C+P), azathioprine (A+P) or cyclophosphamide as a monotherapy (C). The effect of the treatment was evaluated after 6 and 16 weeks. The results were entered consecutively in a sequential analysis. The three treatment regimes were compared mutually as well as with the results of 16 weeks' treatment with C and placebo, published previously. Six weeks' treatment with C+P or A+P was superior to C and at least as efficient as 16 weeks' C treatment. C treatment for 6 weeks was less efficient than 16 weeks' C treatment. The side-effects of the 6 weeks' A+P or C+P treatment were fewer and less serious than those reported from the long-term C treatment.

Adult↗
PubMed1988

Serum and urinary aminoterminal type III procollagen peptide in progressive systemic sclerosis: relationship to sclerodermal involvement, serum hyaluronan and urinary collagen metabolites.

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.

Adult↗
PubMed1987

Injury and repair of smaller muscular and elastic arteries. A light microscopical study on the different healing patterns of rabbit femoral and carotid arteries following dilatation injuries by a balloon catheter.

26 rabbits of the Danish country strain were subjected to mechanical dilatation injury of the left femoral and carotid arteries with Fogarty's embolectomy catheters F2 and F3 respectively. The rabbits were killed 2, 7, 14 and 28 days after the dilatation injury and the arteries examined histologically. Initially both of the arteries exhibited necrosis of the media and infiltration of the vessel wall with neutrophils and mononuclear cells. From day 7, intimal thickening was observed in both types of arteries, progressing in thickness during the later stages. However, thrombosis occurred in the majority of the carotid arteries, whereas this was only infrequently seen in the femoral arteries. In all of the dilated arteries, the elastic laminas were stretched or fragmented and never regained their normal appearance. In the carotid artery, giant cells accumulated around the fragmented elastin and calcified areas, located primarily at the intima-medial border. These changes were never observed in the femoral artery. At the twenty-eight days stage, proliferation of the smooth muscle cells more or less led to restitution of the media in the femoral artery, whereas the carotid artery showed medial restitution only to a lesser extent. The similarities between the injured carotid artery and human temporal arteritis, and the utility of the model as an animal model for the study of temporal arteritis are underlined.

Angioplasty, Balloon↗
PubMed1987

Systemic lupus erythematosus: follow-up study of 148 patients. I: Classification, clinical and laboratory findings, course and outcome.

The present paper is a description of 148 patients with circulating antinuclear antibodies and multisystemic disease filed during 18 years by one of the authors and followed up to date in 1981-83. Seventy-eight per cent of the patients satisfied the 1971 ARA criteria for the classification of systemic lupus erythematosus and 92 per cent fulfilled the 1982 ARA criteria. Eighty-five per cent were women, the mean age at onset of SLE was 32 years. Malar rash and arthritis were early manifestations in 80 per cent of the patients whereas the onset of nephropathy, CNS manifestations, serositis, and peripheral cytopenia was delayed in about half of the patients. Nephropathy and thrombocytopenia were observed particularly in the youngest patients. The mean duration of the observation period was 8 years. The 10-year-survival was 80 per cent. Half of the deaths were presumably unrelated to SLE. The mean ages at entry of patients who died of SLE and of unrelated causes were 30 and 52 years respectively. Eighteen per cent of the deaths were caused by uremia and 18 per cent by infections. The total and the SLE related mortalities were evenly distributed throughout the observation period. The morbidity (incidence of new ARA criteria and other findings indicating active disease) decreased during the first year of observation but rarely subsided completely during the following years. All patients observed for more than 10 years showed evidence of active disease during the rest of the observation period and most showed evidence of renal disease.

Adolescent↗
PubMed1987

Systemic lupus erythematosus. Follow-up study of 148 patients. II: Predictive factors of importance for course and outcome.

The predictive value of a number of clinical and laboratory variables for the mortality of 148 patients with systemic lupus erythematosus (SLE) with a mean observation period of 8 years and a 10-year-survival of 80 per cent was calculated by means of differentiated survival rate analyses and stepwise regression analyses. The predictive power of several variables increased if the calculations were based on deaths caused by SLE rather than on the total mortality rate. The survival rate decreased after 1973 because a diagnosis of SLE was made in some patients with terminal disease who would have remained without a diagnosis before that time. The causes of death and the treatment were identical before and after 1973. The presence of a high number of diagnostic ARA criteria within the first year of observation was a predictor of decreased survival. Severe but non-fatal infections (meningitis, septicemia, pneumonia) significantly reduced the survival rate. Patients with proteinuria and azotemia, within the first 2 years of observation, had a 10-year-survival of 70 per cent. The survival of patients with CNS manifestations was not significantly reduced. The butterfly rash and the presence of lymphopenia were predictors of decreased survival, whereas the presence of DNA antibodies had no predictive value for survival.

Adolescent↗
PubMed1987

Acute phase proteins and clinical synovitis activity in patients with rheumatoid arthritis.

A number of laboratory variables, including Hb., ESR and several phase proteins, fluctuated in concord with the clinical signs of synovitis activity in patients with rheumatoid arthritis during a controlled study of 3 disease-modifying anti-rheumatic drugs (DMARD). The correlation between laboratory variables and clinical synovitis was significant in a large patient population but the correlation coefficients were not of such magnitude that any of the laboratory variables reflected clinical synovitis activity in a reliable manner in the individual patients. In patients treated with azathioprine, the response of the Hb, (and consequently of the ESR), was reduced compared to patients given other DMARD. This phenomenon was caused by the bone marrow suppressing effect of azathioprine. However, the effect of azathioprine on the clinical synovitis activity did not differ from that of the 2 other drugs. Similar results were found by reviewing the literature about controlled trials of DMARD. In the present trial the clinical evaluation was performed under optimal conditions. In daily clinical practice the evaluations of the joints may be less than optimal since they may be performed by different rheumatologists with varying experience. Consequently, it may be difficult to do without the unreliable laboratory variables mentioned in the routine assessments of disease activity, unless the quality of routine evaluations of synovitis activity is improved considerably.

Acute-Phase Proteins↗
PubMed1987

Serum aminoterminal procollagen type III peptide in acute viral hepatitis. A long-term follow-up study.

The development of chronic viral liver disease is associated with increased deposition of connective tissue in the liver. The aminoterminal propeptide of procollagen type III (P-III-NP) is considered to reflect the metabolism of collagen type III, one of the major collagen types in liver fibrosis. The purpose of the present study was to elucidate, whether S-P-III-NP in patients with viral hepatitis was related to injury and repair processes in the liver. S-P-III-NP was determined in a prospective longitudinal study of 63 patients with acute viral hepatitis followed to healing or development of chronic liver disease. Two assays were applied. The P-III-NP Ria-gnost assay, which measures mainly the intact propeptide, and the P-III-NP Fab-assay, in which the antibody exhibits equal affinity to the intact propeptide as well as the degradation product col 1. At the onset of viral hepatitis, S-P-III-NP determined in either assay was equally elevated in the two groups. From the second month of follow-up, significantly higher levels in both assays were observed in patients developing chronic disease. During follow-up, the highest P-III-NP RIA-gnost values were seen in patients with chronic active hepatitis, and active cirrhosis. S-P-III-NP decreased towards normal levels during development of inactive cirrhosis. In the individual patient, S-P-III-NP Ria-gnost was positively related to transaminases. During follow-up of uncomplicated hepatitis a normalization of transaminases occurred before normalization of S-P-III-NP RIA-gnost. Considering, that S-P-III-NP, in contrast to the conventional laboratory variables, reflects the metabolism of type III collagen, it is assumed that determination of S-P-III-NP may provide new information on fibrogenesis in viral liver disease.

Acute Disease↗
PubMed1987

Serum aminoterminal type III procollagen peptide and the 7S domain of type IV collagen in patients with alcohol abuse. Relation to ultrastructural fibrosis in the acinar zone 3 and to serum hyaluronan.

Serum concentrations of the aminoterminal propeptide of type III procollagen and of the 7S domain of type IV collagen, presumed to reflect fibrotic activity in liver tissue, and of the glycosamonoglycan hyaluronan, were obtained from 40 alcohol abusers, at the time of liver biopsy. The serological results were related to morphological findings in liver tissue, i.e. no fibrosis, fibrosis without cirrhosis, micronodular cirrhosis and macronodular cirrhosis, and to ultrastructural indications of perisinusoidal fibrosis in the acinar zone 3. All patients with fibrosis and cirrhosis on light microscopy had elevated serum levels of the type III procollagen peptide as well as of the 7S domain of type IV collagen. However, due to a considerable overlap between the groups, no relations could be demonstrated to the severity of the fibrosis, supporting the assumption that these serological markers reflect the current fibrotic activity and not the amount of fibrotic tissue previously deposited. Among patients without fibrosis on light microscopy, a relation between the propeptide levels and ultrastructural perisinusoidal zone 3 fibrosis was observed, suggesting that type III procollagen peptide may be valuable in detecting very early liver fibrosis. A positive correlation was demonstrated between the serum concentrations of type III procollagen peptide and hyaluronan. As hyaluronan is degraded in the liver endothelial cells, it is suggested that the liver is involved, not only in the synthesis, but also in the degradation of the propeptide.

Adolescent↗
PubMed1987

Giant-cell arteritis. Histological, immunohistochemical and electronmicroscopic studies.

Biopsies from the temporal artery of 32 patients suspected of giant-cell arteritis were evaluated retrospectively by light microscopy, histochemical, and immunohistochemical methods, as well as by transmission electron microscopy (TEM). At the clinical follow-up the 32 patients included four clinical groups: temporal arteritis (8 patients), polymyalgia rheumatica (10 patients), rheumatoid arthritis (4 patients), and a group of miscellaneous diseases unrelated to inflammatory rheumatic diseases (10 patients). There were a number of similarities between age-related alterations in the arteries and the changes in giant-cell arteritis. The most important differences were the inflammatory cellular infiltration of the media, the perifocal accumulation of fibronectin, and the occurrence of deposits of fibrin/fibrinogen and fibrin/fibrinogen degradation products. In addition, alpha-2 macroglobulin, lysozyme and factor VIII were also noted in giant-cell arteritis. The alterations in giant-cell arteritis show a number of similarities to the changes following experimental vascular injury of the rabbit aorta. The nature of the findings in human giant-cell arteritis, as well as the similarity to the experimental arteritis, indicate that giant-cell arteritis may reflect a non-specific reaction to injury, independent of the cause of the disease.

Aged↗
PubMed1987

Combination of methylprednisolone pulse therapy and remission inducing drugs in rheumatoid arthritis.

Thirty patients with rheumatoid arthritis were allocated to either methylprednisolone pulse therapy or placebo at the beginning of treatment with either gold salts, penicillamine, or azathioprine. Methylprednisolone pulse therapy produced an immediate but temporary anti-inflammatory effect lasting for a maximum of four to eight weeks. It also caused a lasting depression of serum IgG, but no effect was observed on the proportion of T and B lymphocytes, proliferative responses, or on concanavalin A induced suppressor cell activity, and there was no effect on the amount of circulating immune complexes. The bone mineral content decreased similarly in the two groups, and methylprednisolone pulses had no effect on the progression of erosions on x rays during an observation period of eight months. A single pulse of methylprednisolone can give a short lasting anti-inflammatory effect but is of little or no value in the long term treatment of rheumatoid arthritis.

Adult↗
PubMed1986

Serum amino-terminal type III procollagen peptide in rheumatoid arthritis. Relationship to disease activity, treatment, and development of joint erosions.

Using 2 radioimmunoassays, increased serum levels of amino-terminal type III procollagen peptide and its degradation products were demonstrated in rheumatoid arthritis patients. Patients with active disease showed higher serum propeptide levels than did patients with inactive disease. Unlike D-penicillamine, azathioprine treatment suppressed the propeptide levels in patients with active disease. A 6-month prospective study showed significantly higher initial serum propeptide levels in patients with erosive progression. The propeptide level reflects disease activity and may be a valuable prognostic marker in rheumatoid arthritis.

Adult↗
PubMed1986

Influence of previous gold treatment and other patient variables on outcome of treatment with disease modifying anti-rheumatic drugs (DMARD) in patients with rheumatoid arthritis.

Based on a 2-year controlled double-blind trial of levamisole, penicillamine, and azathioprine (L, P, and A), a computer aided search for predictive factors of outcome was instituted. Already at month 4 several indicators of synovitis activity were able to discriminate between patients staying in the trial for 24 months and patients whose treatment was discontinued before that time. Patients who had previously received gold therapy responded less favourably to L, P, and A than those who had not received gold. This reduction of response was more pronounced in gold resistant patients than in patients whose gold treatment had been discontinued for other reasons. The only phase protein (of several) with a predictive value was haptoglobin. If, after 4 months of treatment, haptoglobin did not normalize, this finding indicated a lack of response to treatment or a deterioration of synovitis activity during the following 4 months. The response to treatment was not influenced by HLA-types, sex, age, or clinical synovitis, disease duration, functional or anatomical aberrations at the start of treatment. The shape of the response curve as reflected by means of monthly measurements of serum-albumin and ESR was not related to disease duration, HLA-types, or previous gold treatment.

Arthritis, Rheumatoid↗
PubMed1986

Immune-induced dermal connective tissue alterations in rabbits chronically immunized with bovine serum albumin: biochemical studies on collagen, glycosaminoglycans, RNA, and DNA.

Rabbits were chronically immunized by repeated intravenous injections of bovine serum albumin and compared to saline injected controls. All sensitized animals developed antibodies to albumin, but in only a few were circulating immune complexes detected. The dermal biosynthesis of dermatan and heparan sulfate in vivo was significantly restrained following immunization due to a reduced cellular synthesis. The collagen type III/I ratio was significantly repressed in the skin of immunized rabbits, in particular in the acid soluble collagen fraction containing newly formed collagen. Further, the hydroxyproline/DNA ratio, expressing the collagen accumulation per cell, was increased, indicating that the secretion of collagen type I was enhanced. These alterations in the formation and accumulation of matrix components were not correlated to the occurrence of circulating immune complexes or the antibody response. Thus, compared to previous investigations on vascular connective tissue, persistent immunostimulation may alter connective tissue metabolism systemically, and it appears that the metabolism of matrix components characteristic of early connective tissue formation and inflammation is particularly susceptible. These observations may be of significance as regards systemic involvement and chronicity in various inflammatory connective tissue diseases.

Animals↗
PubMed1986

Immune-induced vascular connective tissue alterations in rabbits chronically immunized with bovine serum albumin: biochemical studies on collagen, glycosaminoglycans, RNA, and DNA in normal and injured aorta.

Repeated intravenous injections of bovine serum albumin in rabbits caused a significant reduction in the aortic in vivo biosynthesis of chondroitin-4,6-sulfate, whereas no changes were observed in the synthesis of other glycosaminoglycans nor in the content of collagen. This contrasts the biochemical changes generally seen in acute vascular injury. When experimentally elicited vascular injury and repair processes were induced in chronically immunized rabbits, the proliferative response was greatly inhibited, as reflected by a significant diminution of the DNA amount. Also, the vascular connective tissue matrix repair was restrained: the aortic content of collagen and the collagen type III/I ratio was repressed, and the in vivo biosynthesis of sulfated glycosaminoglycans was markedly reduced. All immunized rabbits developed antibodies to bovine albumin, but in only a few were circulating immune complexes detected. The inhibitory effect of persistent immunostimulation on the nonspecific processes of repair in vascular connective tissue may be of significance as to chronicity of vasculitis, as well as inflammation and repair in general, in inflammatory connective tissue diseases.

Animals↗
PubMed1986

Long-term seropositivity for human T-lymphotropic virus type III in homosexual men without the acquired immunodeficiency syndrome: development of immunologic and clinical abnormalities. A longitudinal study.

The long-term effects of seropositivity for human T-lymphotropic virus type III (HTLV-III) on T-lymphocyte subsets and health status were evaluated in longitudinal studies of 250 initially healthy homosexual men. The relative risk of having an inverted T-lymphocyte helper-to-suppressor ratio rose from 14.3-fold among short-term seropositive subjects (less than 19 months) to 46.9-fold among long-term seropositive subjects (greater than 29 months) in comparison with the risk among seronegative subjects. Overall, 91.7% of long-term seropositive men had inverted ratios, compared with 12.9% of seronegative men. None of the seropositive men who developed an inverted ratio later reestablished a normal ratio. Both decreased T-helper cell number and percentage (p = 0.003) and increased T-suppressor cell number and percentage (p = 0.03) were significantly correlated with duration of seropositivity. Among seropositive persons, lymphadenopathy was a highly significant short-term as well as long-term consequence, whereas diarrhea, oral thrush, and herpes zoster were correlated with long-term seropositivity. Overall, 50% of long-term seropositive men compared with 16% of seronegative men developed at least one of five clinical symptoms (p less than 0.003). We conclude that a high proportion of persons infected with HTLV-III will develop measurable immunologic and clinical abnormalities.

Antibodies, Viral↗
PubMed1986

Prognosis in glomerulonephritis. II. Regression analyses of prognostic factors affecting the course of renal function and the mortality in 395 patients. Calculation of a prognostic model. Report from a Copenhagen study group of renal diseases.

The course of the renal function and mortality were analysed in 395 patients with biopsy-proven glomerulonephritis (GN), using Cox's proportional hazards model. Seventeen clinical, biochemical and histopathological parameters were analysed for prognostic information. The patients were grouped according to their serum creatinine levels. Increase in serum creatinine, decrease in serum creatinine, cure and death were used as endpoints for the analysis. Caplan Meyer curves were made for 7 transitions between different groups and the variables were reduced by a step-wise procedure to a final model. Thirteen of the variables considered offered significant prognostic information (p less than 0.05) for at least one of the transitions. Short duration of disease, young age, non-nephritic urinary sediment and preceding streptococcal infection were predictors of cure. Extracapillary, membranoproliferative and unclassifiable GN, old age and arterial hypertension predicted increase in serum creatinine in patients with low serum creatinine, while male sex, short duration of disease and pathological electrocardiogram favoured a further increase in patients with high serum creatinine. A later decrease in serum creatinine was signified by a preceding streptococcal infection, short duration of disease, absence of arterial hypertension and low urinary protein excretion. Death without uremia was predicted by high age, connective tissue disease and extracapillary GN. Using these parameters and the models, it is possible to make a prognostic forecast for the individual GN patient. Examples of such a forecast are described.

Adult↗