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Biomedical subjects

J G Fjeld

Publications and source records attributed to J G Fjeld.

17 recordsLinked to original sources
PubMed2001

[Immunomodulating treatment in advanced heart failure--effect of intravenous immunoglobulin].

BACKGROUND: Congestive heart failure is characterised by enhanced immune activation. Immune-mediated mechanisms may play a pathogenic role, hence the growing interest in therapeutic regimens that could modulate the immune response in heart failure. MATERIAL AND METHODS: In the present report we discuss the pathogenic role of immunological and inflammatory mediators in the pathophysiology of heart failure and discuss different treatment modalities with focus on our recent study with intravenous immunoglobulin. In that study 40 patients with symptomatic chronic heart failure and left ventricular ejection fraction (LVEF) < 40% were randomised in a double-blind fashion to receive therapy with immunoglobulin or placebo for a total period of 26 weeks. RESULTS: We found that intravenous immunoglobulin, but not placebo, shifted the cytokine balance in an anti-inflammatory direction, and that such a shift was associated with improvement in LVEF by 5 EF units. Functional capacity and haemodynamic variables also improved. INTERPRETATION: Our study supports the hypothesis that immunological variables might be of significant importance in the pathogenesis of heart failure and it suggests a potential for immunomodulating therapy in addition to optimal conventional cardiovascular treatment regimens in such patients. These issues are further discussed in the present article.

Adjuvants, Immunologic↗
PubMed2001

[Voiding problems and urinary tract complications in adolescents and adults with myelomeningocele].

BACKGROUND: The aim of this study was to describe voiding dysfunction and urinary tract complications in a population above 16 years of age with myelomeningocele. MATERIAL AND METHODS: 51 persons were included in the study. Data were obtained by questionnaires, ultrasound and glomerular filtration rate; in those with intact urinary bladder, by cystometry and videocystography. RESULTS: 30 out of 33 persons with intact urinary bladder were incontinent. Those with daily incontinence described this as a major problem. Cystometry concluded with normal detrusor contractions in three, detrusor hyperreflexia in five, and a detrusor hyporeflexia in 25 persons. Three out of 30 had vesicoureteral reflux. Ultrasound showed mild hydronephrosis and/or scarring in three persons. Average glomerular filtration rate was 86% (50-131%). 11 had Bricker diversion and seven continent reservoirs. 15 out of 18 persons with urinary diversion were satisfied with this solution. In persons with urinary diversion, the average glomerular filtration rate was 78% (44-109%). Ultrasound showed hydronephrosis and/or scarring in seven out of 16. Overall, urinary tract infections last year were reported by 56%, and pyelonephritis was more common in those with urinary diversion. INTERPRETATION: Incontinence is a common problem in adults with myelomeningocele. About one third had upper urinary tract changes, but none had renal failure.

Adolescent↗
PubMed2001

[Follow up of urinary tract problems in adults with myelomeningocele].

BACKGROUND: More than 90% of persons with myelomeningocele have a neurogenic bladder disturbance with incontinence and risk of upper urinary tract deterioration. Both aspects need to be considered when planning treatment and follow-up. MATERIAL AND METHODS: The study is based on review of articles and clinical experience. RESULTS: A thorough examination of the patient's voiding methods and incontinence is necessary. Examinations for renal function, reflux and hydroureteronephrosis as well as cystometry should also be carried out. The results of such examinations, together with an assessment of the patient's motor and cognitive function, as well as motivation, will provide a basis for further treatment and follow-up. We suggest a flow-chart for treatment and follow-up of persons above 16 years of age with myelomeningocele. INTERPRETATION: Patients with myelomeningocele should have a thorough examination and an individual plan for treatment and follow-up of their urinary tract dysfunction. Depending on the pathological findings, routine follow-up should be in done intervals from six months to five years.

Adult↗
PubMed2001

Immunomodulating therapy with intravenous immunoglobulin in patients with chronic heart failure.

BACKGROUND: Congestive heart failure (CHF) is characterized by enhanced immune activation, and immune-mediated mechanisms may play a pathogenic role in this disorder. Based on the immunomodulatory effects of intravenous immunoglobulin (IVIG), we hypothesized that IVIG could downregulate inflammatory responses in CHF patients and have potential beneficial effects on the left ventricular ejection fraction (LVEF). METHODS AND RESULTS: Forty patients with chronic symptomatic CHF and LVEF of <40%, stratified according to cause (ie, ischemic and idiopathic dilated cardiomyopathy), were randomized in a double-blind fashion to receive therapy with IVIG or placebo for a total period of 26 weeks. Our main findings were that (1) IVIG, but not placebo, induced a marked rise in plasma levels of the anti-inflammatory mediators interleukin (IL)-10, IL-1 receptor antagonist, and soluble tumor necrosis factor receptors; (2) significantly correlated with these anti-inflammatory effects, IVIG, but not placebo, induced a significant increase in LVEF from 26+/-2% to 31+/-3% (P:<0.01), and this was found independent of the cause of heart failure; and (3) N-terminal pro-atrial natriuretic peptide decreased significantly after induction therapy and continued to decrease toward the end of study during IVIG therapy (P:<0.001) but remained unchanged during placebo. CONCLUSIONS: We demonstrated an IVIG-induced change in the balance between inflammatory and anti-inflammatory cytokines that favored an anti-inflammatory net effect in CHF. This effect was significantly correlated with an improvement in LVEF, suggesting a potential for immunomodulating therapy in addition to optimal conventional cardiovascular treatment regimens in CHF patients.

Adjuvants, Immunologic↗
PubMed2001

Enhanced gene expression of chemokines and their corresponding receptors in mononuclear blood cells in chronic heart failure--modulatory effect of intravenous immunoglobulin.

OBJECTIVES: We sought to study the gene expression of chemokines and their corresponding receptors in mononuclear blood cells (MNCs) from patients with chronic heart failure (CHF), both of which were cross-sectional and longitudinal studies during therapy with intravenous immunoglobulin (IVIg). BACKGROUND: We have recently demonstrated that IVIg improves left ventricular ejection fraction (LVEF) in patients with CHF. Based on the potential pathogenic role of chemokines in CHF, we hypothesized that the beneficial effect of IVIg may be related to a modulatory, effect on the expression of chemokines and their receptors in MNCs. METHODS: We examined: 1) the gene expression of C, CC and CXC chemokines and their receptors in MNCs from 20 patients with CHF and 10 healthy blood donors; and 2) the expression of these genes in MNCs from 20 patients with CHF randomized in a double-blind fashion to therapy with IVIg or placebo for 26 weeks. RESULTS: Our main findings in CHF were: 1) markedly raised gene expression of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and interleukin (IL)-8; 2) enhanced gene expression of their corresponding receptors; 3) modulation in a normal direction of this abnormal chemokine and chemokine receptor gene expression during IVIg, but not during placebo therapy; 4) down-regulation of MIP-1alpha, MIP-1beta and IL-8 during IVIg at the protein level in plasma; and 5) a correlation between down-regulation of MIP-1alpha gene expression and improved LVEF during IVIg therapy. CONCLUSIONS: Our results further support a pathogenic role for chemokines in CHF and suggest that IVIg may represent a novel therapeutic approach, with the potential to improve LVEF in patients with CHF, possibly by modulatory effects on the chemokine network.

Aged↗
PubMed1997

[Scintigraphic localization of ectopic parathyroid tissue].

Ectopic parathyroid adenomas and hyperplastic glands are difficult to locate during surgical exploration. Failure to find and remove them is the most usual cause of surgical failure in the treatment of hyperparathyroidism. Earlier methods of preoperative localization of pathological parathyroid tissue had low sensitivity and were not generally recommended. Recent advances in parathyroid scintigraphy have improved this technique; the sensitivity is now as high as 95% for parathyroid adenomas. In the present study, ectopic parathyroid adenomas and hyperplasia were correctly localized by scintigraphy and were verified surgically in seven patients. Six of the patients had previously undergone ten unsuccessful operations altogether. Preoperative parathyroid scintigraphy might have saved these failed surgical explorations. In a pregnant woman, a mediastinal parathyroid adenoma was correctly localized by preoperative parathyroid scintigraphy. This patient was successfully operated by a sternotomy, and she was the only one of five patients with a mediastinal parathyroid adenoma who escaped unnecessary neck exploration. Preoperative parathyroid scintigraphy may reduce the number of surgical failures in hyperparathyroidism and shorten the operation time by less extensive exploration and thus fewer complications.

Adenoma↗
PubMed1997

Technetium-99m-tetrofosmin for parathyroid scintigraphy: a comparison with sestamibi.

UNLABELLED: Parathyroid scintigraphy with the new myocardial perfusion radiopharmaceutical 99mTc-tetrofosmin was compared with 99mTc-sestamibi scintigraphy using early and delayed imaging. METHODS: The two preparations were administered on different days to the same 16 patients suffering from primary hyperparathyroidism. Anterior view gamma camera planar imaging (10-min acquisition) was performed in the period between 5 min and 3 hr after administration of the radiopharmaceutical. For most of the patients, a pertechnetate image of the thyroid was available for eyeball comparison when reading the tetrofosmin and sestamibi images. Imaging results were compared with those from histopathological examination after surgery. RESULTS: On early images, all the adenomas visualized with sestamibi were equally well seen with tetrofosmin and vice versa. In 6 of 11 scintigraphically detected neck adenomas, delayed imaging improved the adenoma visualization with sestamibi. In contrast, this differential washout was never seen with tetrofosmin. Histopathological examination of excised tissue specimens after neck exploration (15 patients) or thoracotomy (one patient) revealed a parathyroid adenoma in all 16 patients. Our 12 scintigraphic findings were true-positives, while the remaining four scintigraphies were false-negatives, giving a diagnostic sensitivity of 75% with both preparations. The mediastinal adenoma was detected in a patient with a history of two unsuccessful neck explorations and one unsuccessful thoracotomy. CONCLUSION: Tetrofosmin has the same success rate as sestamibi for detection of parathyroid adenomas on scintigrams acquired immediately after injection. In contrast to sestamibi, delayed imaging has no diagnostic impact. Moreover, the thyroid/ parathyroid differential washout of sestamibi failed in 5 of 11 neck adenomas here detected, indicating that delayed sestamibi washout is an unreliable diagnostic criterion. Therefore, whether sestamibi or tetrofosmin is preferred for parathyroid scintigraphy, thyroid scintigraphy seems mandatory.

Adenoma↗
PubMed1996

Pulmonary haemodynamics after single-lung transplantation for end-stage pulmonary parenchymal disease.

In a prospective study, we investigated the effect of single-lung transplantation (SLT) on pulmonary haemodynamics and the relationship between pulmonary hypertension (PH) and the fraction of perfusion to the transplant in patients with end-stage pulmonary parenchymal disease. Twenty four SLT recipients were included in the study, 19 with chronic obstructive pulmonary disease (COPD), two with sarcoidosis and three with fibrosing alveolitis. Spirometry, determination of arterial blood gas values, perfusion scintigraphy and right heart catheterization were performed before and 1, 6, 12 and 24 months after transplantation. Patients with a mean pulmonary artery pressure (Ppa) > or = 20 mmHg before transplantation were defined as having PH (PH group, 15 patients) and the remainder (9 patients) constituted the non-PH group. In the PH group, Ppa and pulmonary vascular resistance (PVR) were significantly decreased after transplantation: 28 +/- 2 to 18 +/- 1 mmHg and 288 to 161 +/- 11 dyne.s-1.cm-5, respectively (mean +/- SEM). In the non-PH group, the haemodynamic parameters were unchanged after transplantation. Over the 2 year follow-up period, no significant change was found in Ppa and PVR, nor any difference between the PH and non-PH group. There was no significant difference between the two groups in terms of pulmonary perfusion to the graft. In conclusion, patients with pulmonary hypertension obtain pulmonary haemodynamics within the normal range after single-lung transplantation. Presence or absence of pulmonary hypertension before transplantation does not influence perfusion to the graft. These findings persist up to 2 yrs, despite the coexistence of an "end-stage" native lung and a lung transplant.

Adult↗
PubMed1993

Animal models for radiolabeled monoclonal antibodies in cancer research.

A review of the different animal tumor model systems used for radiolabeled monoclonal antibody research is given. Problems within the field of radioimmunotargeting are presented, and the tumor models are discussed in relation to the types of problems which can be investigated, and the ability of the models to answer different questions.

Animals↗
PubMed1992

Evaluation of labelled monoclonal antibodies by simultaneous estimation of the association constant, the immunoreactive fraction, and the number of effective binding sites on the specific target.

The reaction between a labelled monoclonal antibody (MoAb) and its specific target is characterised by three parameters: the association constant (Ka) of the labelled MoAb, the number (N) of effective binding sites on the specific target, and the immunoreactive fraction (F) of the labelled MoAb preparation. Immunological binding parameters are usually estimated graphically, by fitting the experimental data to linear equations derived from the first order law of mass action (FLMA) at equilibrium. However, only two parameters can be estimated simultaneously in a two-dimensional plot. Consequently, graphical estimation of Ka, F and N must be performed stepwise, using at least two different plots. The three parameters are interdependent, and therefore a stepwise estimation procedure might give suboptimal results. In order to investigate whether this is a problem of practical significance in the evaluation of labelled MoAbs, a computerised iterative nonlinear least squares (INLSQ) method was applied to estimate the three parameters simultaneously. The binding parameters in reactions between different 125I-labelled MoAbs and different types of targets were significantly changed when a graphical procedure was replaced by the computerised INLSQ method, and the goodness of fit to FLMA was improved. Hence, the nonlinear least squares method is the preferred procedure. Values were affected when only a subset of the data was included in the estimation procedure, indicating some heterogeneity even in these presumably homogeneous MoAb reactions. The radiolabelling procedure was presumed to be the main reason for this heterogeneity.

Alkaline Phosphatase↗
PubMed1992

The binding parameters of radiolabelled monoclonal F (ab')2 and Fab' fragments relative to immunoglobulin G in reactions with surface-bound antigens.

The binding parameters of iodine-125-labelled intact monoclonal immunoglobulin G (IgG), F(ab')2 and Fab' fragments were compared. The study was carried out with the two monoclonal antibodies (MoAbs) K13 and K16 specific for human Ig light chains kappa and lambda, respectively. When testing the 125I-MoAbs against monodisperse polymer particles coated with the specific antigens, the Ka for the F(ab')2 fragments were similar to that for IgG, while the Ka for the Fab' fragments were reduced to 10%-20% of that for IgG. The number N of effective target sites revealed with Fab' was higher than with F(ab')2 and IgG, presumably because less surface area is occupied by the small Fab' molecules. The immunoreactive fraction F ranged according to IgG greater than F(ab')2 greater than Fab'. The explanation of the moderate difference between the Ka of the monoclonal Fab' and the divalent IgG and F(ab')2 was that the divalent molecules were not divalently attached to the particles. When testing the same antibody preparations against human lymphoma cells producing Ig with light chains kappa or lambda, the binding results were less reliable than when particles were utilised, presumably due to antigen shedding. Different MoAbs vary in their loss of immunoreactivity due to enzymatic degradation and the radiolabelling procedure. The preparation of the radiolabelled fragments should therefore be optimized for each MoAb, and evaluation is necessary before injection. Artificial targets with a low leakage of antigen, like the monodisperse polymer particles here applied, are recommended for the in vitro evaluation of the immunoreactivity of labelled MoAb preparations.

Animals↗
PubMed1992

In vivo measurement of the association constant of a radio-labelled monoclonal antibody in experimental immunotargeting.

Exploring the fundamental mechanisms behind the low tumour uptake of labelled monoclonal antibodies (MoAbs) during in vivo immunotargeting, experiments were performed to estimate the in vivo value of the association constant (Ka) in an experimental targeting reaction. An artificial tumour model was utilised, based on diffusion chambers (DC) filled with antigen-coated polymer particles, implanted i.p. in normal, immunocompetent mice (NMRI/BOM). The MoAb H7 with specificity for placental alkaline phosphatase (PLALP) was chosen for this experiment. Each mouse carried two DC, one target DC filled with PLALP-coated particles, and a second control DC with the same amount of uncoated particles. The DC contained escalating doses of particles, ranging from 0.1 mg to 16 mg per DC, with groups of 6-12 animals per dose level. The next day after the implantation, a constant dose of 125I-labelled Fab fragments of H7 was injected i.v. in each mouse. The association constant Ka as measured from the binding data obtained in vivo was not significantly different from the value measured in vitro when the same target DC were incubated with the 125I-Fab in test tubes. This indicates that in vivo impairment of the antibody avidity is not the reason why a relatively low tumour uptake is generally experienced in immunotargeting studies.

Alkaline Phosphatase↗
PubMed1992

Radio-immunotargeting in experimental animal models of intraperitoneal cancer.

The field of immunotargeting, and the challenges met when this technique is applied in experimental animals or in patients, are reviewed. Even with highly specific monoclonal antibodies, non-specific uptake in normal tissues and high background level of unbound radioactivity in blood and extravascular body fluids remain significant problems. Further experimental work in animal model systems is needed to bring this technique from the state of being an experimental method, with limited clinical application, to a routine diagnostic or therapeutic method. Different animal models are available, and their potential for elucidation of the various methodological problems in radio-immunotargeting are discussed in the present paper. In our laboratory, two intraperitoneal models were devised, having relevance for gynecologic and other forms of intraperitoneal malignancies. These models were elaborated with special emphasis on the possibility for exact measurement of important parameters in immunotargeting reactions. In the first model, hybridoma cells are inoculated intraperitoneally to mimic intraperitoneal carcinomatosis, and the monoclonal antibody produced by the hybridoma is used as serum tumor marker. In the second model the tumor cells are contained within intraperitoneally implanted micropore chambers, resembling a localized tumor. An artificial tumor like this allows control with the antigen load in the target, and measurement of the concentration of the injected antibody in the fluid within the target.

Animals↗
PubMed1990

Radioimmunotargeting of human tumour cells in immunocompetent animals.

A tumour model system is reported that for many purposes may be an alternative to xenografted nude mice. The model allows immunotargeting of human tumour cells in immunocompetent animals. The target cells are contained in i.p. diffusion chambers (DC) with micropore membrane walls that are permeable to molecules, including the cell specific monoclonal antibodies (MoAb), but impermeable to cells. Thus, the tumour cells are protected from the host immunocompetent cells. In the work here presented the model was tested in immunocompetent mice and pigs, with tumour cells and antibody preparations that had demonstrated specific targeting in the nude mouse xenograft model. Hence, the DC were filled with cells from the human cell lines Hep-2 (expressing placental alkaline phosphatase, PLALP), or OHS (a sarcoma cell line), and the MoAb preparations injected i.v. were a 125I-labelled Fab fragment of the PLALP specific antibody H7, or a 125I-labelled F(ab')2 fragment of the sarcoma specific antibody TP-1. Specific targeting of the human tumour cells was demonstrated in both mice and pigs. The target: blood ratios were comparable in the two species, reaching a maximum of about 15 after 24 h with the Fab preparation, and a ratio of 25 after 72 h with the F(ab')2. The target uptake relative to injected dose was lower in pigs than in mice, but the difference between the two species was smaller than expected, presumably due to a slower antibody clearance in the pigs than in the mice. An artificial cell targeting system like this has several advantages in the search for solutions to many of the fundamental problems experienced in immunotargeting. Firstly, parallel binding experiments can be carried out in vitro with the same target. Because in vitro results are only influenced by the diffusion into the DC and the immunological binding characteristics of the antibodies, targeting differences between antibody preparations due to these factors can then be distinguished from differences due to pharmacokinetical properties. Secondly, the animals can be implanted with any type and number of target cells, or with antigen negative control cells. Thirdly, and perhaps most important, the system opens a possibility for evaluation of the murine MoAb in xenogenic species, and this may predict the clinical targeting potential better than experiments on mice.

Animals↗
PubMed1989

Immunomagnetic removal of B-lymphoma cells using a novel mono-sized magnetizable polymer bead, M-280, in conjunction with primary IgM and IgG antibodies.

The efficacy of a novel monosized and magnetizable polymer bead, denoted M-280, in immunomagnetic removal of Rael B-lymphoma cells was compared with that of M-450 beads, previously used in bone marrow purging. The M-280 beads which are smaller (diameter 2.8 microns) and contain less iron than the M-450 beads were coated with polyclonal IgG sheep antimouse (SAM) antibody. The two types of immunobeads were equally efficacious when used together with the mouse monoclonal IgG antibodies HH1 or FN1, giving tumor cell depletions of about 3 logs in one cycle of operation. However, when used together with the primary IgM monoclonal antibodies (MoAbs) AB1 or HH2, the new immunobeads were significantly more efficacious than the M-450 immunobeads. To elucidate the underlying mechanism flow cytometric studies and measurements of the binding of the labeled primary MoAbs to the cellular antigens as well as to the immunobeads were carried out. Competition experiments showed that in the case of IgG MoAbs, the SAM beads bind predominantly to the Fc portion, whereas in the case of the IgM MoAbs, the Fab part plays a relatively greater role in the binding. The results indicate that if M-280 immunobeads are used, IgM MoAbs may profitably be included in antibody cocktails together with IgG antibodies in immunomagnetic purging of B-lymphoma cells. They suggest that in the case of cell bound MoAbs, the epitopes on IgG are more accessible to SAM beads than those of surface bound IgM molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1988

In vivo evaluation of radiolabelled antibodies with antigen-coated polymer particles in diffusion chambers.

A method for the evaluation of in vivo immunolocalization of labelled monoclonal antibodies (MoAb) is presented. The technique is an alternative to the nude mouse xenograft system. The antigen reservoir is an intraperitoneal diffusion chamber (DC) filled with a suspension of antigen-coated polymer particles. Intravenously injected 125I-labelled MoAb are allowed to specifically bind to this artificial abdominal 'tumour', which can be removed and measured for radioactivity after animal killing. The model can be used as a preclinical in vivo method for the evaluation of labelled MoAbs prepared for immunodiagnostics or therapy. The DC system permits the amounts of both antibody and antigen to be controlled and antibody access to the antigen within the DC is presumably the same in every animal. The model permits a systematic comparison of different antibodies and antibody fragments, labels and labelling procedures, as well as routes of administration in immunocompetent animals.

Alkaline Phosphatase↗