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Biomedical subjects

M Owsianowski

Publications and source records attributed to M Owsianowski.

At least 19 recordsLinked to original sources
PubMed1998

Management of severe scleroderma with long-term extracorporeal photopheresis.

BACKGROUND: The management of systemic sclerosis remains unsatisfactory. Thus far, the action of extracorporeal photopheresis (ECP) in severe systemic scleroderma has been evaluated in short-term studies, and only limited experience has been obtained with long-term application. OBJECTIVE: The aim of the present study was to evaluate prospectively the long-term effect of ECP in a group of 16 patients suffering from severe scleroderma, showing visceral involvement and progressive clinical course. METHODS: Fourteen patients with systemic scleroderma involving several organs, 1 with CREST syndrome and another with scleroderma-myositis overlap syndrome were treated with ECP over a period of 6-45 months. In 3 cases, gamma-IFN was additionally administered. Skin and visceral involvement were assessed by evaluating a series of clinical criteria and results from laboratory, imaging and functional tests. RESULTS: Overall, clear improvement was encountered in 6 patients, mixed response in 2, stable disease in 3 and continuing progressive course in 5 patients. Four out of 6 patients with improvement were treated with ECP early after onset of scleroderma (< or = 2 years), whereas all patients with a progressive course under ECP had had scleroderma for longer than 2 years. Immunosuppressive drugs previously administered could be reduced or fully withdrawn under ECP treatment in 5 patients, but additional oral medication was introduced in 4 patients due to disease progression. Addition of gamma-IFN to ECP did not reveal further benefit. No side-effects were recorded under ECP treatment. CONCLUSIONS: Based on this observation, we believe that long-term ECP represents an effective treatment modality in severe scleroderma particularly when started early, with stabilization of the disease course and partial remission of the cutaneous findings, whereas visceral involvement, if present, may rarely improve.

Female↗
PubMed1996

[Therapeutic experiences with extracorporeal photopheresis. Technical procedure, follow-up and clinical outcome in 31 skin diseases].

Extracorporeal photophoresis (ECP), a therapeutic modality that has been under investigation for some years, is based on separation of a leucocyte/lymphocyte-enriched cell fraction from the peripheral blood, extracorporeal treatment of the cells with 8-MOP/UVA and subsequent reinfusion of the cells in the patient. Its main effects seem to consist in changes to the immunologic behaviour of the photoinactivated/modulated cells. The immune response of the host is obviously stimulated by this treatment. ECP is normally performed for 4 h per day on 2 consecutive days every 4 weeks. The treatment is well tolerated and causes few side effects. In our department, 1210 ECP treatments were administered to 41 patients between 1990 and 1994 and a preliminary evaluation was performed. These patients included 21 with cutaneous T-cell lymphoma (CTCL), 10 with progressive systemic scleroderma, 4 with chronic graft-versus-host disease and 1 each with pemphigus vulgaris, epidermolysis bullosa acquisita, lupus erythematosus and cutaneous mucinosis. Patients with erythroderma and preserved immunocompetence achieved the best responses of all patients with CTCL. A treatment combining ECP with rIFN-alpha, PUVA and/or radiation was also successful in patients with tumour-stage CTCL and lymph node involvement. Progressive systemic scleroderma responded in more than 50% of our cases. Treatment results were impressive in 4 patients with chronic graft-versus-host disease presenting with sclerodermatous and lichenoid changes of the skin and mucous membranes. A clear improvement was also observed in the patient with pemphigus vulgaris refractory to standard therapies and in another patient with scleromyxoedema (Arndt-Gottron syndrome). The effectiveness of ECP seems to be quite well established in CTCL, but remains to be examined in autoimmune dermatoses. ECP is an attractive addition to the dermatological therapies available but our experience is still preliminary.

Adult↗
PubMed1996

Remission of scleromyxoedema following treatment with extracorporeal photopheresis.

Scleromyxoedema, a disseminated papular and sclerotic variant of lichen myxoedematosus, is a rare disease with a chronic progressive course, and little tendency towards spontaneous remission. The treatment of scleromyxoedema has been largely ineffective. Aggressive chemotherapeutic agents have been used, often leading to therapy-related morbidity and mortality. We report a 41-year-old woman with scleromyxoedema, associated with a monoclonal gammopathy of IgG-kappa type, whose condition almost completely cleared with 12 monthly sessions of extracorporeal photopheresis. The patient had previously not responded to isotretinoin, and chlorambucil with prednisolone.

Adult↗
PubMed1995

Extracorporeal photopheresis--a new approach for the treatment of cutaneous T cell lymphomas.

Extracorporeal photochemotherapy (extracorporeal photopheresis, ECP) is going to become a new alternative in the treatment of cutaneous T cell lymphomas (CTCL), autoimmune disorders, and transplant rejections. After the first promising results in the treatment of CTCL reported in 1987 by Edelson et al. increasing numbers of CTCL patients in a growing number of ECP centers throughout the United States, Europe, and Japan have been successfully treated. Today, it seems that in particular Sézary's syndrome and the erythrodermic variant of mycosis fungoides (MF) respond very well to ECP. Compared to historical controls of MF with lymph node involvement, the median survival of the ECP-treated patients increased from 30 months to up to 60 months. It is our experience that the tumor stage of MF, however, cannot be treated with ECP alone, but is successfully controlled by combination regimens, for example with recombinant interferon alpha. CTCL patients heavily pretreated by polychemotherapy and severe endogenous or iatrogenic immunsuppression do not respond sufficiently and are not good candidates for ECP. The adverse reactions under ECP are well controlled and very low in number. In particular, general immunosuppression by ECP has not been reported so far.

Forecasting↗
PubMed1994

Successful treatment of chronic graft-versus-host disease with extracorporeal photopheresis.

A 43-year-old woman who had undergone allogeneic bone marrow transplant for chronic myeloid leukemia developed chronic GVHD. Despite cyclosporine A and low-dose glucocorticoids and later concomittent PUVA-therapy, chronic GVHD with severe sclerodermatous manifestations including joint contracture and liver damage progressed. The Karnofsky performance score dropped to under 50%. Extracorporeal photopheresis (ECP) instead of PUVA-therapy was started. To our knowledge, we here report the first case of successful treatment of extensive chronic GVHD with ECP.

Adult↗
PubMed1993

Comparison of Borrelia burgdorferi ultrasonicate and whole B, burgdorferi cells as a stimulus for T-cell proliferation and GM-CSF secretion in vitro.

Peripheral blood mononuclear cells (PBMC) from five patients with confirmed Lyme borreliosis (LB) and from seven seronegative healthy subjects were incubated with ultrasonicated sterile-filtrated B. burgdorferi and with whole live Borrelia burgdorferi cells (strain RT1). PBMC culture conditions were 1 x 10(5) PBMC/well/ 10% autologous plasma (AP) and 2 x 10(5) PBMC/well/ 10% pooled human AB-serum (ABS). Recall antigens and Pokeweed mitogen (PWM) served as specific and nonspecific control stimuli. When whole B. burgdorferi cells were used as antigen, both the borreliosis patients (borr) and the healthy subjects (contr) reacted with an elevated stimulation index (SI) and secretion of granulocyte-macrophage colony stimulating factor (GM-CSF) in vitro (SI borr. = 4; SI contr. = 3.7. GM-CSF borr. = 3.1 U/ml; GM-CSF contr. = 5.4 U/ml). A significant difference was observed when the B. burgdorferi sonicate was used. In this case, only the borreliosis patients reacted with an elevated PBMC proliferation and GM-CSF secretion (SI borr. = 6.1; SI contr. = 1.4. GM-CSF borr. = 7.6 U/ml; GM-CSF contr. = 0.3 U/ml) (p < 0.001).

Adult↗
PubMed1993

[In vivo and in vitro detection of borrelia infection in morphea-like skin changes with negative Borrelia serology].

No decision has been made yet as to whether or not the origin of the circumscribed scleroderma (morphea) is spirochetal. We describe a morphea-like skin lesion that developed after a tick bite 10 years ago. The histological investigation showed sclerodermal characteristics and necrobiosis lipoidica of the granulomatous type as well. No antibodies directed against Borrelia burgdorferi could be detected absorbance by a flagellin ELISA or by Western blot analysis. The VDRL, TPHA and FTA absorbance test, Warthin-Starry staining, and cultivation of Borrelia from skin biopsies were negative. The application of a nested polymerase chain reaction (PCR), relying on a combination of flagellin-gene-specific primers, demonstrated for the first time the presence of Borrelia DNA in a morphealike skin lesion. Immunohistological examination of the skin by a monoclonal antibody directed against flagellin was positive. Furthermore, in vitro GM-CSF secretion and lymphocyte proliferation upon stimulation with Borrelia-antigen was elevated and decreased significantly after 3 weeks of treatment with tetracyclines. In this case PCR analysis, immunohistochemistry and cellular immune response confirmed an infection with Borrelia, although no serum antibodies against spirochetal antigens could be detected.

Adolescent↗
PubMed1992

The inhibitory effects of a positive inotropic quinolinone derivative, 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)- quinolinone (OPC-8212), on bone-marrow progenitor cells and peripheral lymphocytes.

3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone (OPC-8212) is a quinolinone derivative with positive inotropic properties. In order to elucidate the effect of OPC-8212 on the haemopoietic system we studied its in vitro effect on bone-marrow progenitor cells (granulocyte/monocyte colony-forming units [CFU-GM] and erythroid burst-forming units [BFU-E]), on the proliferation and secretion of granulocyte/monocyte colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) by peripheral lymphocytes, and on GM-CSF secretion by fibroblasts from healthy individuals. The dose-effect relations of OPC-8212 on CFU-GM proliferation and on lymphocytic GM-CSF secretion showed no effect at very low drug concentrations, with a threshold at the lower end of the therapeutic range and highly significant dose-dependent inhibition at concentrations above that threshold. BFU-E, peripheral lymphocyte proliferation and lymphocytic IFN-gamma secretion were depressed, although to a lesser extent, in a linear dose-dependent fashion. OPC-8212 did not affect GM-CSF secretion by one strain of fibroblasts but reduced it at higher concentrations in assays with another strain of cells. We conclude that direct toxic effects on bone-marrow progenitor cells, in combination with the inhibition of cytokines involved in the regulation of haemopoiesis in certain susceptible individuals, may be responsible for idiosyncratic reactions to OPC-8212.

Bone Marrow↗
PubMed1992

Cytokine-stimulated human dermal microvascular endothelial cells produce interleukin 6--inhibition by hydrocortisone, dexamethasone, and calcitriol.

The effects of lipopolysaccharide (LPS), recombinant human tumor necrosis factor-alpha (TNF), recombinant human interleukin 1-beta (IL-1 beta), and interferon-gamma (IFN-gamma) on IL-6 production were determined by enzyme-linked immunosorbent assay (ELISA) and by Northern blot analysis in cultured human dermal microvascular endothelial cells (HDMEC). Unstimulated HDMEC did not produce significant amounts of IL-6, whereas lipopolysaccharide (LPS), TNF, and IL-1 beta were potent inducers of HDMEC-derived IL-6 production. Treatment with IFN-gamma had no effect. IL-1 beta stimulation resulted in pronounced IL-6 production after 4 h, followed by complete downregulation at the transcriptional level after 24 h. In contrast, LPS and TNF induced prolonged stimulation of IL-6 production by HDMEC as IL-6 mRNA transcripts were still detected after 24 h treatment and IL-6 protein was markedly increased at this timepoint. The effects of hydrocortisone, dexamethasone, calcitriol, acitretin, and cyclosporin A on TNF- or IL-1 beta-induced IL-6 production by HDMEC were determined by ELISA. Both hydrocortisone and dexamethasone dose-dependently inhibited the cytokine-induced IL-6 production, whereas the inhibition by calcitriol was less pronounced. In contrast, acitretin and cyclosporine A had no influence on cytokine-induced HDMEC IL-6 production. These results disclose dermal endothelial cells as a major source for the pro-inflammatory cytokine IL-6, involved in the regulation of inflammatory skin processes. As IL-6 seems to play a key role in the pathogenesis of psoriasis, the beneficial effects of corticosteroids and calcitriol in this disease may partly be explained by their ability to inhibit HDMEC-derived IL-6 production.

Acitretin↗
PubMed1991

Long-term cultured adult human keratinocytes secrete granulocyte-macrophage colony-stimulating factor but not interleukin-3 after cytokine exposure in vitro.

To investigate the secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) and of interleukin-3 (IL-3) by human keratinocytes in vitro, adult human keratinocytes (aHKc) from 3 different donors and a spontaneously transformed keratinocytic line (HaCaT) were cultured and exposed to various cytokines and to the protein kinase C-activating agent phorbol-12-myristate-13-acetate (PMA). GM-CSF and IL-3 were measured by highly specific and sensitive immunoassays. Our findings showed that long-term cultured aHKc and HaCaT cells are capable of secreting GM-CSF but not IL-3 upon cytokine and PMA stimulation. Both interleukin-1 and tumor necrosis factor alpha, which are known to be present in human epidermis, particularly during cutaneous inflammatory processes, were found to stimulate GM-CSF release. Therefore, we conclude that increased GM-CSF levels may play an important role in the interactions between epidermal keratinocytes and blood cells in vivo.

Adult↗
PubMed1990

Lymphokine release, suppressor cell generation, cell surface markers, and cytotoxic activity in cancer patients receiving natural interleukin-2.

We monitored patients treated for 5 days with continuous infusion of increasing doses (3 to 6 x 10(6) U/d) of natural interleukin-2 (IL-2). CD16+, CD25+, and CD56+ cells increased after treatment. Plasma tumor necrosis factor-alpha (TNF-alpha) levels, but not interferon-gamma (IFN-gamma) levels, increased during IL-2 treatment, but spontaneous and IL-2-stimulated TNF-alpha secretion in vitro remained abnormally low. However, mitogen-stimulated TNF-alpha release was normal. Mitogen-stimulated, but not IL-2-stimulated, IFN-gamma release was strongly depressed. Low spontaneous and IL-2-stimulated cytotoxicity on K562 or Daudi increased after treatment. Low suppressor cell generation also normalized after treatment. This appears to be the first reported study of immunologic monitoring of cancer patients treated with natural rather than recombinant IL-2.

Antigens, Differentiation↗
PubMed1982

[Nervous system diseases in large-city population. II. Effect of occupational factors].

The patients of a local outpatient department in a half--million population town have been examined. The rate of organic angiogenic encephalopathies, vasomotor headaches and epilepsy has been three times greater in those performing light work than in the hard-working group. No dependency between the hard work and rate of ischias and lumbago has been found. Operations of productive machines, similarly as the working place microclimatic conditions do not pose a risk of nervous system diseases, except ischias and lumbago which occur more frequently in an occupational group working at low temperature and considerable humidity or at an open air. Likewise, the body position at work significantly affects the rate of ischias and lumbago. Our findings prove that hard work does not pose an additional risk of nervous system diseases. Another conclusion of those investigations is that advantageous microclimate and body position at the working place, possibly accompanied by corrective physical training, are significant in the prevention of ischias and lumbago.

Adolescent↗
PubMed1978

[Nervous system diseases in workers of a large metallurgical plant. II. Impact of occupational factors].

Correlation between some factors connected with work performance in a big metallurgical plant, employing approximately 16000 persons, and the occurrence of nervous system diseases was analysed. It was found that among the most frequent diseases of nervous system cured in neurological dispensary of a big metallurgical plant are: ischias, epilepsy, syndrome of subjective ailments following a past cranio-cerebral trauma and vasomotor headaches. The studies performed did not reveal any clear correlation between the character and arduousness of work and the type of nervous system diseases occurring most frequently in a big industrial (metallurgical) plant. The prevalence of ischias is not significantly dependent on occupational factors. The possibility of continuation of work or necessity to stop working in result of a nervous system disease depend on the type of the disease.

Adult↗
PubMed1977

[Experiences in intensive therapy of apoplectiform pictures of cerebrovascular insufficiency].

Our observations indicate that attention should be paid primarily to the following, in the sequence given, when applying intensive therapy to patients suffering from apoplectiform phenomena of cerebro-vascular insufficiency: keep the respiratory passages open, prevent inflammatory processes, especially bronchopneumonia, give an optimum supply of calories, water and electrolyte to patients in the comatose state, compensate for disturbances in the central regulation of respiration and circulation, combat disturbances of the acid-base balance and prevent cerebral oedema and hyperthermia from central causes. The report was to emphasize the gasometric results of our studies which indicated that 65 per cent of the patients in this group suffer from significant hypoxia and that respiratory alkalosis occurred in 34 per cent. The cause seems to be a disturbance in the respiratory passages which leads to hyperventilation and to subsequent respiratory alkalosis.

Alkalosis, Respiratory↗