Biomedical subjects

M Stoltenberg

Publications and source records attributed to M Stoltenberg.

At least 55 records · Page 3Linked to original sources

PubMed1996

Electron Microscopical Autometallography: Immunogold-Silver Staining (IGSS) and Heavy-Metal Histochemistry

Immunogold-silver staining (IGSS) utilizes a histochemical method called autometallography (AMG) to amplify tiny gold particles to sizes easily visible both in light and electron microscopy. In both applications it is advisable to use the smallest possible gold diameters (1-6 nm) to obtain the highest sensitivity, thus, allowing minute amounts of the target substance to be demonstrated. Gold labels smaller than 10 nm in diameter have been clearly shown to give the highest labeling densities of antigen-antibody binding sites. AMG can be used for the detection of catalytic crystal lattices of metallic gold and silver, and sulfides or selenides of mercury, silver, copper, bismuth, and zinc. The method has its roots in "physical development" technique, transplanted from photography to histology by Liesegang at the beginning of this century. In 1981, a series of papers were published by one of us with the purpose of introducing a reliable and easy-to-handle technique for light microscopical and ultrastructural studies. AMG has a multitude of applications apart from its use in detecting tissue metals. These include the highly sensitive and efficient in situ colloidal gold tracing of peptides, proteins, and amines by immunocytochemistry using the IGSS method, of carbohydrates by lectin IGSS, and of nucleic acids by IGSS in situ hybridization, IGSS in situ polymerase chain reaction, and IGSS in situ self-sustained sequence replication-based amplification (in situ 3SR) techniques, the last two even performing with single-copy sensitivity. Applications of pre- and postembedding AMG for semithin and ultrathin tissue sections are described.

Journal Article↗

PubMed1996

Histochemical localization of zinc ions in the epididymis of the rat.

In the present study, the autometallograpic zinc sulphide technique, an improved version of the original Timm sulphide-silver method, was used. This technique reveals a particular pool of ionic zinc that is chelatable by diethyldithiocarbamate. At the light microscopical level, no reaction for zinc was found in tissues of young prepubertal rats. In adult mating and non-mating rats low zinc staining was found in the head and intermediate epididymis whereas the tail of the epididymis demonstrated high levels of zinc ions. Sections from the epididymal tail revealed a 'compartmentalization', based on pronounced differences in staining intensity along the epididymal ducts. At higher magnification zinc ions were found in the apical part of the principal cell and in the lumen. At the ultrastructural level autometallographic grains were located in vesicles and in lysosome-like structures of the apical parts of the principal cells. The luminal grains were found either associated with sperm cells, with the surface of the large microvilli (stereocilia), or free in the seminal fluid. The variation in content of zinc ions in the epididymal epithelium and lumen suggests that zinc ions are secreted into the lumen from the epididymal tail and may somehow be involved in maturation of the sperm cells.

Animals↗

PubMed1996

Quantitative assessment of synovial inflammation by dynamic gadolinium-enhanced magnetic resonance imaging. A study of the effect of intra-articular methylprednisolone on the rate of early synovial enhancement.

The effect of temporary inflammatory suppression on synovial membrane enhancement, as determined by dynamic and static gadolinium-DTPA enhanced magnetic resonance imaging (MRI), was studied. MRI of 18 arthritic knees was performed before and 1, 7, 30 and 180 days after intra-articular methylprednisolone injection until clinical relapse. MRI of another six knees was performed twice within 2-4 days in order to assess interobserver and inter-MRI variation. The rate of early enhancement of the entire synovial membrane of a pre-selected central sagittal slice (REEsyn,tot), determined by dynamic T1-weighted FLASH MRI, decreased in all knees within the first post-treatment week and remained low during remission, although gradually increasing. In cases of clinical relapse, REEsyn,tot increased to pre-treatment levels. The interobserver plus inter-MRI variation was maximally 27%. The predictive values of a REEsyn,tot below/above 1.0%/s were 0.94 and 0.91, respectively, with respect to the absence/presence of clinical synovitis. Evaluation of small synovial areas revealed marked regional heterogeneity. Static spin echo MRI was not informative. The study indicates that the rate of early synovial enhancement reflects synovial inflammatory activity. Subclinical changes may be revealed. Evaluation of large synovial areas increases reproducibility and reduces the effect of regional heterogeneity. Dynamic MRI may prove a clinically useful measure of synovial inflammation.

Anti-Inflammatory Agents↗

PubMed1996

Quantitative assessment of the synovial membrane in the rheumatoid wrist: an easily obtained MRI score reflects the synovial volume.

Determination of the synovial membrane volume in the rheumatoid arthritis (RA) wrist by gadolinium-DTPA-enhanced MRI is introduced. Moreover, dynamic imaging and an MRI score of synovial hypertrophy, based on gradings in six regions, are evaluated as substitutes of the time-consuming volume calculations. Twenty-six RA wrists were examined. Synovial membrane volumes ranged from 1 to 20 ml (median 9 ml). Synovial hypertrophy scores were highly correlated to synovial volumes (Spearman r = 0.88; P < 10(-8) for uncorrelated values). The volumes and scores were significantly higher in wrists with joint swelling and/or joint tenderness than in wrists without these signs (Mann-Whitney, both P < 0.05). Suboptimal slice selection made dynamic imaging uninformative. MRI allows quantification of the synovial volume in the rheumatoid wrist. The volume is related to clinical signs of inflammation, but may also give information about the cumulated synovial proliferation in the joint. An easily obtained score of synovial hypertrophy reflects the synovial volume and may thus be a useful marker of synovial involvement.

Adult↗

PubMed1996

Bone loss in rheumatoid arthritis. Influence of disease activity, duration of the disease, functional capacity, and corticosteroid treatment.

Axial and appendicular bone mass were studied in 95 patients with rheumatoid arthritis. The aims were to quantify bone mineral density (BMD) and to evaluate the importance of disease activity, duration of disease, functional capacity, and corticosteroid treatment for bone loss in patients with rheumatoid arthritis. The BMD in the lumbar spine (BMDSPINE) did not differ from age-matched healthy controls, but distal forearm BMD (BMDARM) and metacarpal BMD (BMDMCB) were significantly lower in the patients (p < 0.01 and p < 0.001, respectively). Neither BMDSPINE nor BMDMCB were related to the disease activity at the time of investigation. By contrast, BMDARM was decreased in patients with active disease. BMD in any of the three measured locations was not directly correlated to duration of the disease. However, the bone mass in the appendicular skeleton was already decreased within the first two years after the start of the disease. The overall functional capacity in terms of physical activity increased BMD in the axial skeleton. The local functional capacity in terms of grip strength was positively related to BMD in the appendicular skeleton. Patients with severe functional impairment had the lowest BMDARM. The decreased BMD in patients with rheumatoid arthritis seems primarily to be caused by an impaired physical activity which may be related to disease activity. Corticosteroids did not decrease BMD in neither the axial nor the appendicular skeleton. The antiinflammatory effect of steroids lead to clinical improvement, which may counteract the expected negative effect of these drugs on bone in rheumatoid arthritis.

Absorptiometry, Photon↗

PubMed1996

Randomized, placebo controlled trial of withdrawal of slow-acting antirheumatic drugs and of observer bias in rheumatoid arthritis.

Patients with rheumatoid arthritis, in stable treatment with methotrexate, penicillamine, or sulfasalazine, were randomized in a double-blind fashion either to continuation of their usual treatment or to placebo. 112 patients were included; 52 patients who refused participation had no more severe disease than the others. The patients felt worse on placebo than on active drug (p = 0.002). The mean differences in number of tender, painful and swollen joints after one month were 2.4 (p = 0.08), 3.0 (p = 0.12) and 2.2 (p = 0.03), respectively. Treatment failure occurred for 42 patients of whom 33 received placebo (p = 0.000,001). There was no difference in the severity of side effects (p = 0.91). The patients guessed their treatment correctly more often than expected (p = 0.02) because of the perceived effect. None of the two observers guessed better than chance, and there were no differences between the observers' evaluations of the joints. The effect of slow-acting antirheumatic drugs was unequivocal and no observer bias occurred.

Aged↗

PubMed1996

Changes in synovial membrane and joint effusion volumes after intraarticular methylprednisolone. Quantitative assessment of inflammatory and destructive changes in arthritis by MRI.

OBJECTIVE: To evaluate synovial membrane volumes, effusion volumes, and cartilage and bone erosion scores determined by magnetic resonance imaging (MRI) as markers of disease activity and severity in arthritis. METHODS: Gadolinium-DTPA enhanced MRI of 18 arthritic knees was performed before and 1, 7, 30 and 180 days after intraarticular methylprednisolone injection until clinical relapse. Intraobserver, interobserver, and inter-MRI variations were determined from 2 successive MRI of another 6 knees. RESULTS: In all knees synovial membrane and effusion volumes decreased within the first posttreatment week (median decrease 49 and 65%, respectively), and remained low during remission. Synovial volumes, but not effusion volumes, increased to pretreatment levels in case of clinical relapse, indicating that synovial volumes were most important to the clinical appearance. The intraobserver + interobserver + inter-MRI variation was maximally 26%. Total volumes and volumes in a selected sagittal slice were highly statistically correlated. The duration of clinical remission in patients with rheumatoid arthritis (RA) was significantly inversely correlated to the pretreatment synovial volume (both total and "one slice" volumes), but not to the effusion volume, MRI or radiography scores of erosions or any clinical/laboratory variables. Cartilage and bone erosions, invisible by radiography, were visualized by MRI. No progressive erosive changes were observed. CONCLUSION: MRI-determined synovial and effusion volumes and MRI scores of cartilage and bone erosions are reproducible and may be sensitive measures of disease activity and severity in RA. The synovial volume may rather than the effusion volume determine clinical appearance. Both are influenced by the present inflammatory activity. The pretreatment synovial volume may have predictive value to treatment outcome in RA.

Adult↗

PubMed1995

Glucocorticoids inhibit the synthesis rate of type III collagen, but do not affect the hepatic clearance of its aminoterminal propeptide (PIIINP).

The aminoterminal propeptide of type III procollagen (PIIINP) is a marker of type III collagen metabolism. The serum concentration of PIIINP is increased during inflammation, probably reflecting stimulated biosynthesis of type III collagen. Serum PIIINP decreases during glucocorticoid treatment. This has been interpreted as an inhibited biosynthesis of type III collagen. However, circulating PIIINP is extracted by the liver, and the decrease in serum PIIINP may also be caused by an increased hepatic elimination. In the present study we investigated the influence of intravenous methylprednisolone on the serum PIIINP level in pigs combined with a simultaneous determination of the hepatic extraction of PIIINP. The serum level of PIIINP decreased by approximately 30% within 2 h following glucocorticoid injection (p < 0.01). The initial hepatic extraction ratio of PIIINP was 0.15 (range 0.05-0.33) and neither changed after administration of methylprednisolone nor differ from that of the controls. Injection of methylprednisolone did not influence the gel filtration profile. The results of this study confirm the previous finding of serum PIIINP being decreased following glucocorticoid administration, but disprove the hypothesis that alterations in the liver extraction of PIIINP explain the decrease.

Amino Acid Sequence↗

PubMed1995

Effect of intraarticular osmic acid on synovial membrane volume and inflammation, determined by magnetic resonance imaging.

The changes in MR-determined synovial membrane volume, early synovial enhancement, and cartilage and bone erosions after osmic acid knee synovectomy were studied. Gadolinium-DTPA enhanced magnetic resonance imaging (MRI) of 18 knees with persistent arthritis was performed before and 1 month after treatment. The synovial membrane volume was significantly reduced (median -52%) in all 9 patients brought into clinical remission (p < 0.01), while no significant change was found in patients with clinical relapse. The early synovial enhancement was not significantly changed. MRI revealed progressive erosive changes in 2 patients. The time of relapse was correlated to a MR-erosion score, but not to early synovial enhancement or volumes of synovium or effusion (Spearman tests). MRI-determined synovial membrane volumes and early synovial enhancement may be objective quantitative markers of inflammation. MR-scores of cartilage and bone erosions are sensitive to progressive changes occurring within a month.

Adult↗

PubMed1995

The accuracy of MRI-determined synovial membrane and joint effusion volumes in arthritis. A comparison of pre- and post-aspiration volumes.

Magnetic resonance imaging (MRI) of 18 knees of patients with arthritis was performed before and immediately after arthrocentesis. Pre- and post-aspiration volumes were calculated by adding the outlined areas of synovium/effusion from a continuous series of gadolinium-DTPA-enhanced 5 mm transversal T1-weighted MR-images. The difference between MRI-determined and syringe-determined volumes of aspirated joint fluid was 0-7 ml, median 2 ml, corresponding to 0-18%, median 7%, of the pre-aspiration effusion volume. Synovial membrane volumes, determined before and after arthrocentesis varied 0-10 ml, median 3 ml (0-17%, median 7%). No significant systematic misinterpretation of the borderline between joint fluid and synovium was found. We conclude that effusion volumes and in all probability also synovial membrane volumes, can be determined by MRI with a maximal analytical error of approximately 20%. The acceptable accuracy of the method encourages further studies of the value of effusion and synovial membrane volumes as markers of the activity and/or severity of joint inflammation.

Adult↗

PubMed1995

Scoring of synovial membrane hypertrophy and bone erosions by MR imaging in clinically active and inactive rheumatoid arthritis of the wrist.

MRI-scores of synovial membrane hypertrophy and bone erosions of the RA-wrist are introduced. Gadolinium-DTPA enhanced magnetic resonance imaging (MRI) and conventional radiography (CR) of the wrist were performed in 16 patients with rheumatoid arthritis (RA) and 3 healthy controls. A MRI-score of synovial membrane hypertrophy was obtained by summation of gradings of synovial hypertrophy in 6 regions of the wrist. The score was significantly higher in wrists with than in wrists without clinical signs of active arthritis. The score was 0 in all healthy controls. Each bone of the wrist was assessed by MRI and CR with respect to bone erosions. Bone erosions were detected by MRI in 14 wrists in contrast to only 6 wrists by CR. In all patients the erosions were more numerous on MRI. The introduced methods may be useful quantitative measures of synovitis and early joint destruction in RA.

Adult↗

PubMed1994

How to detect gold, silver and mercury in human brain and other tissues by autometallographic silver amplification.

Gold, silver, mercury and zinc bind chemically to sulphide or selenide ions and create crystal lattices that can be detected in histological sections by a silver amplification technique called autometallography (AMG). The technique specifically magnifies such nanometer-sized catalytic crystals. For each metal, a detailed protocol has been worked out. If several different AMG metals/metal molecules are present in the same tissue, it is possible to distinguish one from another. The AMG technique is based on the capability of small crystal lattices of the aforementioned metals and metal molecules to initiate AMG silver amplification. Electrons released from adhering hydroquinone molecules reduce silver ions that are integrally connected with the crystal lattices. In this manner, particles consisting of only a few atoms of, say, gold, or molecules of mercury selenide (Figure 1), can be silver amplified to a size at which they can be detected in the electron microscope, or even further to dimensions that can be observed in the light microscope. Thus the AMG technique opens up the possibility of visualizing gold, e.g. in the nervous system of rheumatic patients who have been treated with aurothiomalate. Mercury can similarly be visualized in tissues from individuals who have been exposed to mercury, either through leaching from amalgam dental fillings, through eating fish, or by occupational exposure, and silver in the central (CNS) and peripheral nervous systems (PNS) and other tissues from individuals exposed to silver in one form or another. In the future, the possibility of demonstrating vesicular zinc, a particular pool of endogenous zinc that is found in terminals of zinc-enriched neurons (ZEN neurons), might prove valuable for pathological interpretation of diseases such as Alzheimer's disease. The vesicular zinc, present in some of the synaptic vesicles of ZEN neuron terminals, is most impressively demonstrated by AMG in telencephalic structures. It is becoming increasingly indisputable that vesicular zinc is related to synaptic activity influencing or modulating facilitatory synapses. ZEN neurons are probably a sub-population of glutaminergic neurons. A technique for the post-mortem demonstration of vesicular zinc in terminals of ZEN neurons in human brains is therefore urgently required.

Animals↗

PubMed1993

Serum concentrations of type I and III procollagen propeptides in healthy children and girls with central precocious puberty during treatment with gonadotropin-releasing hormone analog and cyproterone acetate.

Serum levels of type I and III procollagen propeptides (s-PICP and s-PIIINP) were measured in 466 healthy school children and in 23 girls with central precocious puberty (CPP) during GnRH analog and cyproterone acetate therapy, using two commercially available RIAs. In normal children, s-PICP and s-PIIINP changed significantly with age and pubertal development stages. For s-PIIINP, a peak was seen at 12 yr for girls and 13 yr for boys; no peak could be discerned for s-PICP. The prepubertal (Tanner stage 1) s-PICP value (mean +/- SD) for girls was 374 +/- 132 micrograms/L, the midpubertal value (stage 3) was 442 +/- 135 micrograms/L, and the postpubertal value (stage 5) was 203 +/- 103 micrograms/L. The mean s-PIIINP levels for girls were 9.1 +/- 2.4, 15.0 +/- 4.3, and 6.8 +/- 3.1 micrograms/L, respectively. For boys, levels were 362 +/- 119, 544 +/- 138, and 359 +/- 256 micrograms/L for s-PICP and 8.5 +/- 2.2, 14.5 +/- 5.0, and 8.6 +/- 3.8 micrograms/L for s-PIIINP (P < 0.001 for both propeptides in both boys and girls). There was, however, a large variation in normal values for both propeptides within the age groups and pubertal stages. There was a significant correlation of s-PICP and s-PIIINP levels to height velocity in girls (r = 0.35; P < 0.001 and r = 0.33; P < 0.001, respectively), while in boys, only s-PIIINP showed significant correlation to height velocity (r = 0.40; P < 0.001). In untreated girls with CPP, serum levels of s-PIIINP were elevated [PIIINP SD score (SDS), 2.13]. Levels of s-PICP were normal (PICP SDS, 0.39). Levels of both propeptides decreased within 2 months after initiation of therapy and remained below initial values (P < 0.01). The decrease in s-PIIINP after 2 months of therapy showed a significant correlation with the fall in height velocity SDS for chronological age after 6 months of therapy (r = 0.64; P < 0.01). We conclude that s-PIIINP and, to a lesser degree, s-PICP reflect growth in normal children, but due to the large variation, both propeptides seem unsuitable as markers for screening of growth disorders in children.

Adolescent↗

PubMed1991

Early thrombolytic treatment reduces analgesic requirement in patients with myocardial infarction.

The duration and amount of analgesics required were investigated in 67 patients with myocardial infarction treated with intravenous recombinant tissue-type plasminogen activator (rtPA) or placebo in a randomized double-blind trial. Infusion of rtPA (100 mg)/placebo was started within 5 h after the onset of symptoms, and the requirement for analgesics during the following 48 h was recorded. Sixty-seven per cent of the 30 rtPA-treated patients required analgesic treatment for less than 6 h, compared to 38% of the 37 patients in the placebo group (P = 0.04). During the study period, patients in the rtPA group used the equivalent of 5.3 mg (median value) intravenous morphine, which was significantly less than the 11.2 mg used in the placebo group (P = 0.04). In conclusion, the present study suggests that early thrombolysis with intravenous rtPA reduces the amount and duration of analgesic treatment required by patients with myocardial infarction.

Adult↗

PubMed1990

[Treatment of unstable angina pectoris. A questionnaire study].

Questionnaires about therapy in unstable angina pectoris were sent to 63 Danish medical departments and were answered by 52 departments (82.5%). Nitroglycerin is commonly used but only in half of the departments is Nitroglycerin administered intravenously. Calcium-receptor-blockers are used in more departments (65%) than beta-receptor-blockers (35%) (p less than 0.05). Five departments use thrombolytic therapy along local guidelines. All recommend aspirin as prophylaxis against thrombosis and 63% recommend the therapy to be continued for life. An exercise test is always performed during hospital stay in 1/3 of the departments while the rest of the departments often wait till after the patient has been discharged. The estimate of frequency of coronary angiography varied considerably: from less than 5% to 100%. The frequency of coronary angiography was stated to be higher in Copenhagen and Aarhus (median 50%, interval 10-100%) than in the rest of the country (median 15%, interval less than 5-75%) (p less than 0.01).

Adrenergic beta-Antagonists↗

PubMed1990

[Use of fibrinolytics in the treatment of acute myocardial infarction in Denmark. A questionnaire study].

Questionnaires were sent to all Danish departments admitting patients with acute myocardial infarction (AMI) in order to investigate the attitudes of the departments to thrombolytic therapy in AMI. Two questionnaires were used: one with few questions which was answered by all 68 departments, and a more comprehensive questionnaire which was answered by 51 departments. The study shows that thrombolytic therapy now is use in all departments as opposed to 25% two years ago. In connection with introduction of thrombolytic therapy scientific studies are performed in 75% of the departments. In all departments, streptokinase (SK) is the drug of first choice and recombinant tissue plasminogen activator (rt-PA) is used in 2/3 of the departments in cases where SK-antibodies are suspected.

Denmark↗

PubMedDate not supplied

Stressors and stress management--1 month after myocardial infarction.

Stressors and stress management behaviors reported by 52 myocardial infarction (MI) patients were identified from a content analysis of transcriptions of nurse/patient/spouse interactions that took place 30 days postinfarction. Subjects defined stress primarily in terms of distress related to appraisals of harm, loss, or threat. Stressors and stress management behaviors varied, although subjects were similar in age and occupation and were in the same phase of recovery. Most stressors related to recent myocardial infarction and pertained to thoughts and feelings more than to external events. Others, related to family and/or work, were ongoing before the MI. Stress management behaviors comprised a continuum of physical, cognitive, and verbal behaviors ranging from active to passive. Avoidance of situations, ignoring situations, expressing feelings, and thinking things through were the four major modes of stress management behaviors. Implications for rehabilitation nursing practice are identified.

Adaptation, Psychological↗

PubMedDate not supplied

Autometallographic detection of silver in hypothalamic neurons of rats exposed to silver nitrate.

The silver amplification technique, autometallography, has been used to reveal silver accumulation in neurons in the hypothalamus of male Wistar-Kyoto rats. Silver penetrated the blood-brain barrier after exposure to silver nitrate, and differences in staining intensity were found between the hypothalamic nuclei. When using light microscopy, the silver staining of the hypothalamic neurons was highly heterogeneous. Silver was detected exclusively in lysosomes of the loaded neurons. Aspects of this heterogeneous localization are discussed in relation to the distribution of autometallographically developed gold and mercury.

Animals↗