[Hematological paraneoplastic syndromes].
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Hematologic Diseases↗
Biomedical subjects
G Mazur
Publications and source records attributed to G Mazur.
Disseminated nocardiosis as a complication of Evans' syndrome.
Nocardiosis is an opportunistic infection caused by gram-positive, weakly acid-fast filamentous aerobic organisms. Three species cause infection in man: N. asteroides, N. brasiliensis, and N. caviae, the first one being the most common. With increased use of immunosuppressive therapy for various autoimmune diseases, opportunistic infection by Nocardia has increasingly been reported. N. asteroides infections manifest in various ways; the lungs, skin, and brain are the organs most frequently involved. We describe a patient with Evans' syndrome, a disease requiring long-term immunosuppression, who acquired systemic nocardiosis. The infection was primarily pulmonary, misdiagnosed as tuberculosis, with subsequent hematogenous dissemination to the skin and central nervous system. The diagnosis of cerebral involvement was difficult to prove, as the patient presented with stroke-like episodes. After a positive blood culture was obtained, antibiotic therapy was introduced. The patient's condition deteriorated and the brain with infiltration of the meninges, lungs, skin, and kidneys. Nocardia is an important but often overlooked opportunistic infectious agent in immunocompromised hosts, causing diagnostic and therapeutic problems. As the mortality of cerebral nocardiosis is greater than 80%, early diagnosis and appropriate therapy are crucial.
Adult↗
Inhibition of factor XIIIa-mediated incorporation of fibronectin into fibrin by pulmonary surfactant.
Intra-alveolar deposition of exudated plasma proteins is a hallmark of acute and chronic inflammatory lung diseases. In particular, fibrin and fibronectin may provide a primary matrix for fibrotic lung remodeling in the alveolar compartment. The present study was undertaken to explore the effect of two surfactant preparations on the incorporation of fibronectin into fibrin. We observed that surfactant phospholipids are associated with insoluble fibrin, factor XIIIa-cross-linked fibrin, and cross-linked fibrin with incorporated fibronectin. Factor XIIIa-mediated binding of fibronectin to fibrin was noticeably altered in the presence of surfactant. Coincubation with two different commercially available surfactants but not with dipalmitoylphosphatidylcholine alone resulted in a reduction of fibronectin incorporation into fibrin clots by approximately one-third. This effect was not dependent on the calcium concentration. We conclude that 1) factor XIIIa-cross-linked fibrin-fibronectin is able to incorporate surfactant phospholipids in amounts comparable to fibrin clots without fibronectin and 2) the binding of fibronectin to fibrin is partially inhibited in the presence of pulmonary surfactant.
1,2-Dipalmitoylphosphatidylcholine↗
Bronchiolitis obliterans syndrome after (heart-)lung transplantation. Impaired antiprotease defense and increased oxidant activity.
Increased numbers of neutrophils are a common finding in bronchoalveolar lavage fluid (BALF) samples obtained from patients after (heart-)lung transplantation [(H)LTX]. Since proteases and reactive oxygen species secreted by neutrophils are capable of causing substantial damage to the lung tissue if not counterbalanced by the antiprotease and antioxidant screen, we hypothesized that neutrophil products may play a role in the development of obliterative bronchiolitis (OB). A total of 72 BALF samples obtained from 33 patients after (H)LTX were evaluated. Sixteen of these patients were suffering from bronchiolitis obliterans syndrome (BOS) at the time of bronchoalveolar lavage (BAL). As a control, BALF samples from 17 healthy volunteers were analyzed. Anti-neutrophil elastase (NE) activity was quantified by a titration assay. Concentrations of alpha(1)-protease inhibitor (API), secretory leukocyte protease inhibitor (SLPI), NE-API complex, and myeloperoxidase (MPO) were measured by ELISA. Oxidized methionine [Met(O)] was quantified by high-performance liquid chromatography (HPLC). Epithelial lining fluid (ELF) from patients suffering from BOS showed significantly increased neutrophil counts, significantly elevated concentrations of NE-API complex and Met(O), and a significant decrease in the concentration of SLPI. Furthermore, a trend toward an increased NE activity and MPO concentration was observed. These findings suggest that neutrophils may be involved in the development of BOS.
Bronchiolitis Obliterans↗
[Treatment of symptoms in the course of neutropenia].
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Anti-Bacterial Agents↗
[Hematological problems in patients with bronchial cancer].
Four patients with lung cancer and hematological disorders occurring in different stages of the disease are presented. In three out of them cancer metastases were found prior to the discovery of the primary focus. In two patients those metastases were localized in the bone marrow resulting in the hematological picture of the myelodysplastic syndrome and osteomyelofibrosis. In one of them acute lymphoblastic leukemia developed after short-lasting remission involving the regression of bone marrow metastases of the cancer. In one patient lymph node enlargement, constitutional symptoms and laboratory signs of inflammation led to the preliminary diagnosis of Hodgkin disease. In the remaining patient acute leukemia resistant to chemotherapy developed 34 month after the diagnosis of lung cancer. Our observations point to the necessity of the through diagnosis in every case of hematologic abnormalities of unknown origin and the search of a possible underlying malignancy.
Adult↗
Comparative loss of activity of recombinant secretory leukoprotease inhibitor and alpha 1-protease inhibitor caused by different forms of oxidative stress.
Secretory leukoprotease inhibitor (SLPI) and alpha 1-protease inhibitor (alpha 1-PI) are powerful antiproteases currently under investigation for their potential to protect the lung from neutrophil elastase (NE). The aim of this study was to determine whether the recombinant form of SLPI (rSLPI) and alpha 1-PI show different grades of loss of inhibitory activity when exposed to reactive oxygen metabolites. We incubated rSLPI and alpha 1-PI with N-chlorosuccinimide (NCS), chloramines, activated polymorphonuclear leucocytes (PMNs) and activated alveolar macrophages (AMs). Under all conditions evaluated, both antiproteases were partially inactivated. The resulting anti-NE activity of rSLPI was not significantly different from that of alpha 1-PI after exposure to NCS (p > 0.5), chloramines (p > 0.6), activated PMNs (p > 0.07) and activated AMs (p > 0.9). In conclusion, recombinant secretory leukoprotease inhibitor and alpha 1-protease inhibitor lose antineutrophil elastase activity to a similar extent when exposed to conditions that may be present in inflammatory lung disorders.
Animals↗
[Triiodothyroxine (T3), thyroxine (T4), thyreotropine (TSH) and myoglobin levels in patients with myasthenia gravis].
T3, T4, TSH and myoglobin levels were determined in 14 patients with myasthenia gravis and compared with thirty one healthy control subjects. Significant decrease of myoglobin concentration and increase T3, T4 levels as compared to control group was found. TSH concentration was in normal range. Duration of myasthenia, level of disease (according to Osserman classification) and kind of therapy not influenced on detectable variations myoglobin, T3, T4 and TSH concentration.
Adult↗
[Hematologic changes in stomach cancer].
Haematologic disturbances in 13 cases of gastric cancer are described. All the patients had anemia of different origin. Increased leukocytosis was observed in half of the cases, leukemic reaction in one third. Hemolysis was present in 50% of cases. Thrombocytopenia coexisted most frequently with disseminated intravascular coagulation in 4 patients. Bone metastases were visualised as osteolytic foci with radiological methods or increased capture of isotopic marker in the bones under scintigraphic examination. Under the microscope neoplastic metastases were found in bone marrow smears of 5 patients. All patients displayed symptoms of gastric ulcer disease acute or chronic phase. In some cases only repeated gastroscopic examination and mucosa biopsy was the only way to confirm cancer. In other cases the diagnosis was made after the histopathologic examination of the resected stomach, in still others by a section.
Adenocarcinoma↗
Intermittent 2-hour intravenous infusions of 2-chlorodeoxyadenosine in the treatment of 110 patients with refractory or previously untreated B-cell chronic lymphocytic leukemia.
The purpose of our study was to determine the effectiveness of 2-CdA in 2-hour intravenous infusions in the treatment of B-CLL. One hundred and ten patients with B-CLL received 1 to 10 courses of 2-CdA (median 2.5) at a dosage of 0.12 mg/kg daily for 5 consecutive days. Eighteen of them were untreated and 92 relapsed or became refractory to previous therapeutic modalities. Complete remission (CR) was achieved in 8 (7.3%) and partial remission (PR) in 35 patients (31.8%) giving an overall response rate of 39.1%. In 3 patients, cross-resistance to fludarabine was noticed. Toxic effects of 2-CdA were more frequently observed in previously treated patients. Hemorrhagic complications due to drug-induced thrombocytopenia were noticed in 25 (22.7%) and severe infections including sepsis in 14 (12.7%) patients.
Adult↗
[Involvement of the larynx during the course of plasmocytoma].
A case is reported of 63 year old male with disseminated multiple myeloma treated for more than 2.5 year with chemotherapy and radiotherapy. After partial remission lasting for 8 months secondary myeloma infiltration closing nearly the whole hypoglottical part of the larynx and upper part of the trachea developed. Surgical excision of the infiltration was technically impossible to perform. An intensive cytostatic treatment was ineffective but radiotherapy seemed to give some results. Patient suddenly died during morning toilet.
Combined Modality Therapy↗
Impaired CD25 expression and soluble CD25-IL-2R alpha receptor release by anti-CD3 stimulated peripheral blood mononuclear cells in Hodgkin's disease patients.
We examined 22 patients in active phase of Hodgkin's disease (HD), 12 patients in complete clinical remission and 16 healthy subjects for their responsiveness to anti-CD3 stimulation as measured by CD25 antigen expression on peripheral blood mononuclear cells (PBMC) and production of CD25-IL-2R alpha. Simultaneously, the serum levels of soluble interleukin 2 receptor alpha (sIL-2R alpha) were estimated. Our studies indicate that PBMC in patients in active phase and in clinical remission have impaired ability to express CD25 antigen after stimulation with anti-CD3 monoclonal antibody. Similarly, the levels of sIL-2R alpha in culture supernatants were significantly lower in both groups of patients: in active phase and clinical remission compared with the controls. In contrast, the mean serum level of sIL-2R alpha was significantly higher in active phase of the disease compared to that found in patients in clinical remission and controls. Our studies suggest that sIL-2R alpha, derived from PBMC, is not the source of increased levels of sIL-2R alpha found in the sera of patients in active phase of HD. Their synthesis and secretion/shedding most probably takes place in the involved tissues.
Adolescent↗
Decreased production of interferon gamma by anti-CD3 monoclonal antibody and interleukin-2-stimulated peripheral blood mononuclear cells in Hodgkin's disease.
We have examined the production of interferon (IFN) gamma by peripheral blood mononuclear cells (PBMC) in 22 patients with Hodgkin's disease (HD) in active phase of the disease, 12 patients in clinical remission and 16 healthy subjects. The level of IFN gamma in supernatants of PBMC stimulated for 72 h with anti-CD3 monoclonal antibody (mAb), measured by sandwich enzyme immunoassay (ELISA) was 50.4 +/- 2.3 U/ml in active phase; 137.0 +/- 7.4 U/ml in clinical remission patients; and 520.0 +/- 10.0 U/ml in the controls; the difference between the groups was statistically significant. Co-stimulation with interleukin-2 (rIL-2) markedly amplified production of IFN gamma. The mean levels were 220.8 +/- 7.0 U/ml, 590.7 +/- 3.6 U/ml and 2111.1 +/- 17.3 U/ml in active phase HD, clinical remission and controls, respectively, the difference between groups was statistically significant. The patients showed the same kinetic pattern as healthy individuals. Our results indicate that patients with HD have severely impaired TCR/CD3 activation pathway resulting in significantly depressed IFN gamma response to anti-CD3 mAb and anti-CD3 + rIL-2 in vitro stimulation and provide support for the possible clinical use of IFN gamma as an immunopotentiating agent in patients with HD.
Adult↗
[Haematologic changes in gastritic cancer].
Haematologic disturbances in 13 cases of gastric cancer are described. All the patients had anemia of different origin. Increased leukocytosis was observed in half of the cases, leukaemia reaction in one third. Haemolysis was present in 50% of cases. Thrombocytopenia coexisted most frequently with disseminated intravascular coagulation in 4 patients. Bone metastases were visualised as osteolytic foci with radiological methods or increased capture of isotopic marker in the bones under scintigraphic examination. Under the microscope neoplastic metastases were found in bone marrow smears of 5 patients. All patients displayed symptoms of gastric ulcer disease acute or chronic phase. In some cases only repeated gastroscopic examination and mucosa biopsy was the only way to confirm cancer. In other cases the diagnosis was made after the histopathologic examination of the resected stomach, in still others by a section.
Adult↗
[Hypothermia during chemotherapy for lymphomas].
There are only few reports in the literature on the occurrence of hypothermia after chemotherapy. It occurred after various cytostatics and lasted for few hours to several days. Our material consisted of 11 patients with malignant lymphoma who were given chemotherapy protocols including cisplatin. In 5 patients (2 with Hodgkin's disease and 3 with non-Hodgkin's lymphoma) who had high fever, after treatment the temperature decreased down to 34.3 degrees C. Hypothermia disappeared spontaneously after few days. The drug responsible for this effect in our patients was cisplatin.
Adult↗
[Immunopathogenesis of extrinsic allergic alveolitis].
Inhalation of a variety of organic dusts may cause the onset of hypersensitivity pneumonitis (HP) finally leading to irreversible pulmonary fibrosis in some individuals. So far, the pathogenesis of HP remains partially unclear. Besides patient-related factors this is probably attributable to the complex composition of the causative dusts: in addition to specific antigens that may induce type III and type IV reactions they contain a variety of additional components like particles and toxins with the ability to promote several antigen-independent reactions. During an acute episode of HP a marked alveolitis dominated by polymorphonuclear cells develops. As we showed these polymorphonuclear cells are in an activated state and may therefore cause pronounced damage in the lung interstitium. Based on these and other findings we believe that polymorphonuclear cells are of predominant importance for the pathogenesis of HP.
Acute Disease↗
Occupational sensitization to Plasmopara viticola.
Molds of the class of Oomycetes are of allergologic importance in special cases. However, probes are not commercially available for diagnostic purposes. Our case report is based on the medical history of a greenhouse worker who had atopic syndrome. He handled pure cultures of defined fungi and plants. A sensitization to pseudo mildew growing on grapevine (Plasmopara viticola) was found. Skin prick test and histamine release test results were positive when extract of P. viticola was used. Detection of IgE reactivities against pseudo mildew via binding tests, Western blot analysis, and isoelectric focusing immunoblot confirmed the diagnosis. To our knowledge these results demonstrate for the second time a sensitization to Oomycetes.
Adult↗
Analysis of B-cell epitopes in the N-terminal region of Chi t I component III using monoclonal antibodies.
The hemoglobins of the midge Chironomus thummi thummi (Chi t I) are known to cause immediate-type hypersensitivity reactions in humans. Further knowledge of the antigenic sites of such allergens will provide new therapeutic approaches. The aim of our study was to identify and characterize linear B-cell epitopes of the hemoglobin component III of Chi t I (136 amino acid residues). Using the antigenic index algorithm of Jameson and Wolf (Jameson and Wolf (1988) Comput. Appl. Biosci. 4, 181-186), three linear binding sequences of this allergen molecule were predicted. Two mouse monoclonal antibodies (mAbs 3 and 6) raised against purified Chi t I component III were investigated by ELISA for their binding to nine synthetic peptides 19-21 residues in length, covering nearly the whole sequence of component III. MAb 6 recognized only one peptide (11-30) while mAb 3 bound to both N-terminal peptides (1-19 and 11-30), suggesting that the antibody binding site is located in the overlapping region. This assumption could be confirmed in ELISA with solid phase-bound recombinant peptides (RP) as well as in inhibition studies with free tryptic peptides indicating that identification of these linear B-cell epitopes is neither influenced by the method of peptide production nor by the kind of used immunoassay. To define the essential amino acid residues we investigated mAbs with solid phase-bound overlapping octamers. In the case of mAb 3, amino acids experimentally identified as essential for antibody binding (aa 13-17) are identical with those residues predicted as a B-cell epitope with the antigenic index of Jameson and Wolf.
Allergens↗