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Biomedical subjects

H Deicher

Publications and source records attributed to H Deicher.

At least 91 records · Page 5Linked to original sources

PET and MR imaging in a neuro-Behçet syndrome.

Positron emission tomography (PET) and magnetic resonance imaging (MRI) studies were performed on a case of neuro-Behçet's syndrome. In accordance with the clinical signs, FDG PET (using 18F-labeled 2-F-2'-desoxyglucose) revealed disseminated storage defects in the cerebrum and cerebellum. Focal regions of enhanced signal intensity were demonstrated in the parietal white matter of the cerebrum in T2-weighted images and in the brain stem by MRI.

Adult↗

Effect of interleukin-2 on the ex vivo growth of human myeloma cells.

Short-term cultures containing bone marrow mononuclear cells from multiple myeloma patients secrete monoclonal immunoglobulin- and beta 2-microglobulin into the supernatant, which can be measured quantitatively in an enzyme-linked immunosorbant assay. In this system, the addition of interleukin-2 was shown to induce tumor cell regression in the cultures from 10 out of 14 multiple myeloma patients in a dose-dependent manner. Marker analyses of culture cell populations indicate that OKT3 antibody or interleukin-2 did not directly act on the malignant clone but augmented autologous T lymphocytes, which were responsible for the regression of tumor cells in the cultures.

Antigens, Differentiation, T-Lymphocyte↗

Recombinant human interferon (IFN) alpha-2b in chronic myelogenous leukaemia: dose dependency of response and frequency of neutralizing anti-interferon antibodies.

Twenty-seven patients with Philadelphia chromosome positive chronic myelogenous leukaemia in the chronic phase were treated with low doses of recombinant interferon (IFN) alpha-2b. Ten patients entered a complete and six a partial haematologic remission with a median duration of 5.8 and 9.1 months respectively. Five minor cytogenetic responses were observed. These results are inferior compared to other studies with higher interferon-doses. Fever was an acute side effect after injection of IFN, limb pains and fatigue occurred protractedly. Haematologic side effects, nonspecific EEG changes, weight loss, and development of pulmonary infiltrates were observed in later periods of the treatment. Eight patients developed neutralizing anti-IFN antibodies after 4.2-20.4 months (median 12.8 months). Anti-IFN antibodies were associated with relapse or refractoriness to IFN treatment: five out of nine patients with rising WBC after initial fall had antibodies, while four did not. Two out of four patients with primary non-response had IFN-antibodies. These results may indicate a serious problem in the long-term treatment of CML with recombinant interferon.

Adolescent↗

MX homologous protein in mononuclear cells from patients with systemic lupus erythematosus.

The 76-kd human interferon (IFN)-induced MX protein is the homolog to the murine protein, which is necessary and sufficient to provide adequate resistance to influenza virus infection in murine cells and in mice. Fifty-one patients with systemic lupus erythematosus (SLE) were screened for the presence of the MX homolog in mononuclear cells and for IFN and anti-IFN antibodies in serum. In 47 of 51 patients, significant levels of the MX homolog were found, while only 15 of 51 patients had measurable alpha-IFN in their serum. The IFN activity found in these sera was characterized as a partially acid-labile alpha-IFN, by means of acid-stability cross-reactivity on heterologous cells, trypsin sensitivity, and neutralization by homologous or heterologous antisera. Four of the patients had no detectable MX homolog in their leukocytes; 3 of these 4 possessed an anti-alpha-IFN antibody that was able to neutralize both a natural alpha-IFN preparation and the acid-labile IFN in SLE sera. Also, acid-labile alpha-IFN-containing SLE sera induced the MX homolog in vitro in mononuclear cells from healthy donors. These observations suggest that endogenously produced alpha-IFN is responsible for the observed induction of the MX homolog in SLE and that the IFN system is activated in more than 90% of SLE patients.

Antibodies↗

Suppression of polyclonal B cell proliferation mediated by supernatants from human myeloma bone marrow cell cultures.

For functional characterization and semi-quantitative estimation of soluble regulator factors influencing polyclonal B cell proliferation and differentiation, we established two assays. One of the assays measures enhancement or inhibition of proliferation from purified human spleen B lymphocytes, and the other one the effect of soluble factors on CESS-cell differentiation. We found no difference concerning regulator factors for B cell differentiation between bone marrow cell culture supernatants from multiple myeloma (MM) patients and from controls, whereas significantly higher suppressor activity on polyclonal B cell proliferation could be detected in the former group of supernatants. The extent of such determined suppressor activity in vitro correlated with the amount of polyclonal serum IgM of the corresponding patients. These results indicate that one or several soluble suppressor factors may be involved in immunoregulatory mechanisms responsible for the humoral immunodeficiency observed in MM patients.

B-Lymphocytes↗

Humoral response to recombinant interferon-alpha 2b in patients receiving recombinant interferon-alpha 2b therapy.

Twenty-seven patients in the chronic phase of a Philadelphia chromosome-positive chronic myelogenic leukemia (CML) underwent a monotherapy with recombinant interferon-alpha 2b (rIFN-alpha 2b), receiving a mean dose of 3 x 5 Mio. IU per week. Eight of the 27 patients developed both rIFN-alpha 2b-binding and -neutralizing antibodies during therapy. Sera of these patients abrogated both antiviral and antiproliferative activities of rIFN-alpha 2b, but not of nIFN-beta or rIFN gamma. Only one serum neutralized nIFN-alpha. The IFN binding and neutralizing titers rose during therapy, while a decrease occurred over months after cessation of therapy. The IgG fraction obtained by DEAE chromatography contained more than 90% of the IFN-neutralizing capacity of the purified sera. This result strongly suggested that IgG antibodies are responsible for the IFN-alpha-neutralizing activity.

Antibodies↗

Intralesional interferon-alpha therapy in advanced malignant melanoma.

Fifty-one evaluable patients with histologically proven metastatic melanoma and at least one skin metastasis were treated intralesionally with interferon-alpha (IFN-alpha). Twenty-six of the patients were given highly purified natural IFN-alpha 6 Mio. IU three times per week. Twenty-five patients were given 10 Mio. IU three times per week of a recombinant IFN-alpha 2b (rIFN-alpha 2b). All patients were examined for systemic and local responses to this treatment. The systemic responses consisted of nine objective remissions, each of which lasted from 2 to 18 or more months. There were 24 complete or partial local responses. Forty-two of the 51 patients had at least two skin metastases so that IFN-injected and noninjected tumor sites could be compared. The difference between systemic and local efficacy was highly significant statistically (P = 0.0004). The results show that IFN-alpha has clinically observable antitumor activity in malignant melanoma.

Adult↗

Presence of interferon and anti-interferon in patients with systemic lupus erythematosus.

Sera from 61 patients with systemic lupus erythematosus (SLE) were serially screened over a period of at least 2 years for IFN and anti-IFN antibodies. IFN concentrations were measured both with a cytopathic effect assay and a more sensitive radioimmunoassay. Of the patients 15% (9/61) had IFN in their serum at one or more occasions as measured in the bioassay (greater than or equal to 6 IU/ml); employing a RIA (greater than or equal to 1 IU/ml) 28% (17/61) of the patients studied were positive for IFN-alpha. Fifteen patients had a measurable interferonemia over 2-16 months; only two patients had detectable IFN in their serum at only one occasion. In five patients, hourly and daily variations of the IFN titer as measured by RIA were found to amount to less than 80%. The IFN activity found in these sera was characterized as IFN-alpha by means of acid stability, cross-reactivity on heterologous cells, trypsin sensitivity, and neutralization by homologous and heterologous antisera. IFN antibodies were quantified with a neutralization bioassay, an ELISA, and a radioimmunoassay. Of the 61 patients 5% (3) possessed high titers of anti-IFN antibodies which persisted over 2 years. The IFN-alpha antibody positive patients had an inactive form of the disease over years without visceral involvement but decreased serum complement levels (C4, C3, CH50) and repeated episodes of Quincke-like edema.

Antibodies↗

Induction and maintenance therapy in multiple myeloma: a multicenter trial of MP versus VCMP.

In a prospective multicenter trial, 320 untreated myeloma patients of stage II and III were randomized for remission induction into two groups receiving six monthly courses of either MP or VCMP treatment. Response rates were equal in both groups: 72% remission, 21% no change, 7% progress for patients evaluable by TCM changes and 56% remission, 11% no change, 33% progress for BJ- and non-secretory myelomas. The overall survival rate was 60% after 4 years. An unexpected finding was the significantly longer survival of MP treated patients compared to the VCMP group. After successful remission induction, patients were randomized into one group receiving maintenance treatment using the induction scheme q 8 weeks, and another group without further chemotherapy. Although patients in the latter group relapsed significantly earlier, differences between both groups concerning acquired resistance to first line therapy or survival have not been noticed to date.

Adult↗

High incidence of monoclonal immunoglobulins in patients after liver or heart transplantation.

Sera from 56 recipients of liver or heart transplants were investigated for monoclonal immunoglobulins (mIg) by immunofixation electrophoresis (IFE) at different times during 4 years after transplantation. Transient, changing, or stable mIgs were found in 18 patients. A significantly increased mIg incidence was observed in heart Tx patients, patients over 40 years of age, and those receiving azathioprine or antithymocyte globulin in addition to prednisolone and cyclosporine as immunosuppressive treatment. No correlations could be found between the presence of mIg and the number of rejection episodes or intercurrent infections. Such serum mIg represent monoclones of at least 1 x 10(9) cells of B lymphocyte lineage that apparently proliferate without adequate suppressive control. Since immunosuppressed allograft recipients are at risk of developing B cell lymphomas, such monoclones may be regarded as prelymphomas necessitating a careful follow-up in these patients.

Antibodies, Monoclonal↗

VBAMDex chemotherapy in advanced multiple myeloma.

In a phase II study 28 patients with advanced multiple myeloma were treated with a five drug regimen consisting of vincristine, BCNU, adriamycin, melphalan and dexamethasone. 11 out of 13 patients without prior chemotherapy showed significant remissions (greater than 25% tumor cells mass reduction), 7 of them had more than 75% TCM reduction. Out of 15 additional patients resistant to previous chemotherapy, 13 had significant remissions, including 9 patients with greater than 75% TCM reduction. No tumor progression was observed in either group of patients. The median follow-up of all patients was 12.75 months. 4 patients relapsed. Toxicity mainly related to the bone marrow was observed in 14 patients. This regimen might offer a promising alternative for the treatment of advanced multiple myeloma, but still has to be tested in a prospective randomized trial.

Antineoplastic Combined Chemotherapy Protocols↗

[Induction and maintenance therapy in multiple myeloma. Results of a multicenter study].

In a prospective study by the German Myeloma Treatment Group, 320 untreated patients with multiple myeloma, stage II and III, were randomized into 2 groups receiving courses of either MP or VCMP as induction treatment every 6 months. 72% of the patients evaluable by TCM changes remitted, 21% showed a no change, and progress occurred in 7%. The corresponding results in BJ and nonsecretory myelomas were 56% remissions, 11% no change, 33% progress. The response rates were equal in both treatment groups. The overall survival was 60% after 4 years. However, MP-treated patients lived significantly longer than patients in the VCMP group. After successful remission induction, patients were randomized into one group with maintenance treatment using the induction scheme Q 8 weeks, and another group without further chemotherapy. Although the relapse rate of the latter group was significantly higher, differences between both groups concerning survival have not been observed.

Antineoplastic Combined Chemotherapy Protocols↗

Clinical features and prognosis of patients with possible ankylosing spondylitis. Results of a 10-year followup.

Eighty-eight patients with possible ankylosing spondylitis (AS) were selected for this followup study. They showed normal or at most suspicious radiographic findings of the sacroiliac joints. After 5 years' followup, 24, and after 10 years 32 patients (59% of the 54 finally available, 36% of the 88 original patients) had definite AS. In 12 individuals, AS could be excluded. Of the 10 remaining patients, 6 still had possible, and 4 had undifferentiated spondyloarthropathy. A comparison between HLA-B27 positive and negative patients showed a significantly increased frequency of definite AS or possible and undifferentiated spondyloarthropathy (p less than 0.05) in the group of HLA-B27 positive patients. The development of AS was characterized by a prolonged course: radiological sacroiliitis became evident after at least 9 +/- 6 years, radiological signs of spinal involvement after 11 +/- 6 years mean disease duration. After 18 +/- 6 years 25 (78%) of 32 patients with AS still maintained good or sufficient functional capacity, indicating a good functional prognosis in the great majority of the patients.

Adult↗

[Low-dose alpha-interferon treatment of hairy cell leukemia].

Fifteen patients (36-71 years old) with histologically proven hairy-cell leukemia were treated with a low dose of IFN-alpha. The treatment consisted of 1 million I.U. given daily subcutaneously. After 1 month the dose was reduced in all patients 1 million I.U. thrice weekly. Four of the 15 patients have been splenectomized, with two patients receiving chemotherapy prior to the IFN treatment. All patients exhibited at least one cytopenia. The IFN treatment was well tolerated. Only two of the 15 patients experienced mild fever after the first injection, one patient had apathia and mild somnolence after 2 months of therapy. At present 15 patients can be evaluated: 6-18 months after start of therapy two patients showed a complete response with normalization of both peripheral blood and bone marrow, 10 patients experienced a partial response, while one patient showed a slight response with improvement of the thrombocyte count only. Two patients showed no improvement after 3 months of therapy; these patients are presently being treated with 5 million I.U. IFN-alpha thrice weekly. In spite of the low number of patients these data strongly indicate that IFN-alpha-2 is effective in hairy-cell leukemia at this low dose.

Adult↗