Biomedical subjects

I Brink

Publications and source records attributed to I Brink.

28 records · Page 2Linked to original sources

PubMed2000

Diagnosis and monitoring of central nervous system involvement in systemic lupus erythematosus: value of F-18 fluorodeoxyglucose PET.

OBJECTIVE: To investigate prospectively abnormalities of brain glucose utilisation in relation to major or minor neuropsychiatric symptoms in systemic lupus erythematosus (SLE). METHODS: Positron emission tomography (PET) using F-18-labelled fluorodeoxyglucose was performed in 28 patients with SLE. Patients were classified as having severe neuropsychiatric manifestations (seizures, focal neurological deficits, acute confusional states, mood disorders) (n=12), or mild neuropsychiatric manifestations (headache, reactive depression, cognitive dysfunction, anxiety disorders) (n=11) and five patients without signs of central nervous system (CNS) involvement. Ten clinically and neurologically healthy volunteers served as controls. In 26 patients magnetic resonance imaging (MRI) was performed and autoantibodies against CNS tissue, ribosomal P protein and cardiolipin were measured. In 14 patients follow up PET scans were performed after a mean (SD) period of 11.6 (9.5) months. RESULTS: PET scans showed hypometabolism in at least one brain region in all patients with severe or mild CNS symptoms (100%) as compared with patients without cerebral symptoms (40%) (p<0.0025). Parieto-occipital regions were most commonly affected (96%), followed by parietal regions (32%). In contrast, MRI images were abnormal in only 11 of 22 patients (50%) with neuropsychiatric symptoms and in one of four patients (25%) without symptoms. In 12 of 14 patients examined in follow up PET scans persistence, improvement or worsening of cerebral symptoms were associated with unchanged, decreased or increased brain hypometabolism, respectively. No significant correlation was found between PET or MRI findings and autoantibody profiles. CONCLUSIONS: PET imaging represents a sensitive tool to detect manifest or subclinical CNS involvement in SLE and PET findings correlate well with the clinical course of disease.

Adolescent↗

PubMed2000

Alterations of cerebral glucose metabolism indicate progress to severe morphological brain lesions in neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric systemic lupus erythematosus (SLE) is frequently associated with deficits in brain glucose metabolism, even if morphological imaging by magnetic resonance imaging (MRI) shows no abnormalities. In these patients it is unclear whether or not the changes of brain metabolism measured by F-18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) may progress to lesions of cerebral structure. We describe a 20-year-old woman with SLE who presented with depression, headache and impairment of memory. Initially, a cranial MRI was negative, but FDG-PET revealed significant hypometabolism in the frontal and parieto-temporo-occipital regions on both sides as well as hypermetabolism in the nuclei caudati. Within two months the patient developed an acute confusional state, seizures, visual disturbances and cranial MRI became positive showing hyperintensities at the basal ganglia and the temporo-occipital regions. Focal cerebral symptoms responded to treatment with high dose corticosteroids and brain lesions in MRI disappeared. However, a second FDG-PET showed persistent hypometabolism at frontal regions in accordance with the persistence of subclinical depression. To our knowledge, this is the first SLE case report showing that functional brain lesions visualized by FDG-PET may be a risk factor for subsequent structural brain damage seen in MRI. Thus, FDG-PET may help to verify cerebral involvement of SLE earlier than MRI.

Adult↗

PubMed1999

Effects of anti-CD4 antibodies on the release of IL-6 and TNF-alpha in whole blood samples from patients with systemic lupus erythematosus.

Anti-CD4 antibodies have been recently introduced into the therapy of various autoimmune diseases, among them systemic lupus erythematosus (SLE). Their modes of action are not yet fully understood. Interference with cytokine release may be one possible mechanism. Therefore, the effects of anti-CD4 antibodies on the cytokine release of IL-6 (interleukin-6) and TNF-alpha (tumor necrosis factor alpha) were investigated in a whole blood culture system. Basal and phytohemagglutin/lipopolysaccharide (PHA/LPS)-stimulated cytokine patterns were compared to cytokine release after the addition of anti-CD4 antibodies (MAX.16H5) or methylprednisolone in short time whole blood cell culture systems from 12 patients with active SLE, 23 patients with inactive SLE and 12 healthy volunteers. TNF-alpha and IL-6 concentrations were determined in the supernatants by ELISA. High disease activity correlated with an increased production of proinflammatory cytokines. Cell cultures of patients with inactive SLE showed a diminished capacity to respond to mitogenic stimulation. Anti-CD4 antibodies added in vitro suppressed significantly the unstimulated production of IL-6 (P<0.02) in the cell cultures of patients with active SLE and in the PHA/LPS-stimulated cell cultures from both groups of SLE patients (both P<0.001) and healthy volunteers (P<0.01). However, MAX.16H5 did not affect the release of TNF-alpha. In control samples methylprednisolone considerably reduced stimulated and unstimulated IL-6 and TNF-alpha production in all SLE patients, irrespective of the disease state, and in all healthy controls. These data indicate that the proinflammatory cytokines are involved in the pathogenesis of SLE. It is assumed that anti-CD4 antibodies, which can be effective in the treatment of highly active lupus patients, may act via their influence on cytokine release. The decrease of the proinflammatory cytokines IL-6 under therapy with MAX.16H5 could explain the observations of clinical trials and animal studies which showed a reduction of inflammatory parameters and diminished production of autoantibodies following treatment with anti-CD4 antibodies.

Antibodies, Monoclonal↗

PubMed1999

[Imaging of an adrenal cortex carcinoma and its metastasis with FDG-PET].

We describe the case of a 42-year old female patient with a carcinoma of the adrenal cortex. The primary tumor was resected without residual tumor tissue; only two weeks later there was a new large tumor formation in the adrenal gland's bed. PET-investigation showed the large local recurrency, multiple lung-, and liver-metastasis, so that no further operative therapy was performed. FDG-PET seems to be suitable for diagnosis and staging of adrenal cortex carcinoma in one single examination.

Adrenal Cortex Neoplasms↗

PubMed1996

Cyclin D1 messenger RNA is induced in microglia rather than neurons following transient forebrain ischaemia.

Following 30 min of forebrain ischaemia in the rat, delayed neuronal death occurs in the CA1 sector of the hippocampus within two to three days, whereas neurons in other selectively vulnerable regions, such as the dorsolateral striatum, die within 6-12 h. In this study, we investigated cyclin D1 expression, which codes for a regulatory protein in cell cycle regulation, but it is also induced in sympathetic neurons undergoing programmed cell death. Cyclin D1 messenger RNA could not be detected by in situ hybridization techniques in brains of control rats, but was found at one and two days after ischaemia in regions of the dorsolateral striatum with neuronal degeneration. DNA fragmentation in this region, identified by the terminal transferase biotinylated-UTP nick end labelling (TUNEL) procedure, was observed from 6 h after ischaemia onward. In the hippocampus, increased levels of cyclin D1 messenger RNA were found at two and three days after ischaemia in the striatum pyramidale of the CA1 sector. This expression was associated with the occurrence of neuronal damage and TUNEL-stained neurons. By seven days cyclin D1 messenger RNA was found in hardly any brain structure. There was no temporospatial overlap of cyclin D1 expression with the expression of the immediate-early genes c-fos, c-jun, and mkp-1, a result which is clearly distinct from findings in sympathetic ganglion neurons undergoing programmed cell death. These results do not suggest a role for cyclin D1 in neuronal cell death following transient forebrain ischaemia. The similarity of the cyclin D1 expression profile with that of the microglia-specific CR3 complement receptor beta-subunit messenger RNA, and the results of combined in situ hybridization and microglia-specific immunohistochemistry suggest that microglia are the source of cyclin D1 messenger RNA in the postischaemic brain. Since cyclin D1 codes for a critical regulatory protein for progression of the G0 to G1 phase in the cell cycle and we did not observe prominent occurrence of DNA fragmentation in microglial cells in the hippocampus at time points when cyclin D1 messenger RNA was found, we suggest that cyclin D1 induction is involved in the onset of microglial cell proliferation.

Animals↗

PubMed1995

Effects of methylprednisolone and 21-aminosteroids on mitogen-induced interleukin-6 and tumor necrosis factor-alpha production in human peripheral blood mononuclear cells.

The compounds U-74389G (16-desmethyl tirilazad) and U-74500A are two of the novel series of nonglucocorticoid 21-aminosteroids (or lazaroids) which mimic the high-dose neuroprotective pharmacology of the glucocorticoid methylprednisolone (MP) in the injured CNS. Despite structural analogies to MP, it has been shown previously for a variety of endpoints that lazaroids are devoid of classical glucocorticoid effects. Our objective here was to measure the immunosuppressive effects of these lazaroids directly. Specifically, we have compared the in vitro effects of MP, U-74389G, and U-74500A on the mitogen-induced cytokine production in human peripheral blood mononuclear cells, which is known to be very sensitive and perhaps the most clinically relevant parameter reflecting immunomodulation. We show that, in contrast to the glucocorticoid MP, both lazaroids at therapeutically relevant concentrations have no significant inhibitory effects on stimulated interleukin-6 and tumor necrosis factor-alpha production, neither via residual glucocorticoid receptor-mediated activities nor via direct physicochemical effects on cellular membranes. These results strongly support the view that lazaroids lack glucocorticoid activities, but rather exert their tissue protective effects via mechanisms that are independent of glucocorticoid-receptor binding.

Cells, Cultured↗

PubMed1994

Modulation of cytokine expression by hypericum extract.

The effect of hypericum extract LI 160 on the stimulated cytokine expression was investigated in vitro in a whole blood culture system. Blood samples were taken from five healthy volunteers and four depressive patients. The release of interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) was measured quantitatively after an incubation time of 24 hours on microtiter plates. A massive suppression of the interleukin-6 release was found for PHA-stimulated hypericum extract. Possible relations to the antidepressive effects of hypericum extract are discussed.

Antidepressive Agents↗

PubMed1990

[Cytotoxic effect on human keratinocytes caused by anti-Ro-(SS-A) antibodies and UVA in vitro].

It is supposed that anti-Ro(SS-A) antibodies play an important role in the development of photosensitive skin disease in subacute cutaneous lupus erythematosus and neonatal lupus erythematosus. The aim of the experiments was to demonstrate that anti-Ro(SS-A) antibodies and UVA-light cause a cytotoxic effect on human keratinocytes in vitro. Keratinocytes are irradiated with UVA-light in presence of serum containing anti-Ro(SS-A) antibodies (62 E, ELISA). After application of 20 J/cm2 UVA-light only 48.5% of the irradiated cells are still vital (standard trypan blue exclusions test). Examination by scanning electron microscopy shows plain depressions on the surface of the keratinocytes, which were irradiated in presence of anti-Ro(SS-A) antibodies.

Antibodies, Antinuclear↗

PubMedDate not supplied

Reproducibility of PET brain mapping of cancer patients.

Twenty German cancer patients (56.9+/-12.7 years old) without brain metastasis underwent neurological PET. The acquired brain data were compared to the data of ten age and sex-matched controls (53.6+/-15. 7). Scores of Zung's Self-rating Depression Scale (SDS) obtained from 15 out of the 20 patients suggested they might be mildly depressed. Scores of Taylor's Manifest Anxiety Scale (MAS), used for additional psychological evaluation, were close to normal distribution. Hypometabolic areas in the German cancer patients were compared with those demonstrated in our previous study in Japanese cancer patients. Common findings in both studies were observed in the limbic structures, such as the anterior and posterior cingulate gyri, the basolateral frontal cortices, as well as in the basal ganglia (especially the caudate nucleus) and frontal cortex. These results are in accordance with many previous PET studies on major depression. The results show that the positron emission tomography and (18)F-fluoro-deoxyglucose ((18)FDG-PET) brain mapping results could be partially reproduced, and suggest that PET brain mapping of cancer patients has a potential clinical application to the field of psycho-oncology and cancer patient care.

Adult↗

PubMedDate not supplied

High grade cardiac lymphoma vitality monitoring by gadolinium-enhanced magnetic resonance imaging (MRI).

Primary cardiac lymphoma (PCL) is a rare disorder with a poor prognosis and response monitoring is often difficult. Delay in the diagnosis and infiltration of cardiac structures contribute to the unfavorable prognosis. We report on a 76-year-old woman who was diagnosed as having an immunoblastic B-cell PCL according to a histology attained by catheter-guided biopsy. Systemic chemotherapy with six cycles of CHOP (Cyclophosphamide, Doxorubicine, Vincristine = Oncovine, Prednisone), combined with the monoclonal anti-CD20 antibody Rituximab induced only a partial remission, based solely on monitoring of tumor size. However, cardiac gadolinium-enhanced magnetic resonance imaging (CMR) disclosed a reduced lymphoma perfusion and, therefore, indicated decreased tumor vitality. Nine months after the final treatment, the cardiac tumor further decreased to 10% of the initial size, and the patient is in sustained remission as monitored by CMR and validated by florine-18 fluorodeoxyglucose positron emission tomography (PET). Determination of PCL perfusion was, in our case, beneficial for clinical decision making on additional therapy.

Aged↗