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Biomedical subjects

P Imbach

Publications and source records attributed to P Imbach.

At least 73 records · Page 4Linked to original sources

Autologous bone-marrow transplantation for Burkitt's lymphoma: marrow purging with anti-Y 29/55 monoclonal antibody and complement.

Reinfusion of undetected tumour cells is a possible cause of relapse after autologous bone-marrow transplantation. In this paper, a system for in-vitro purging of bone marrow is presented which involves the B-cell neoplasia-associated monoclonal antibody anti-Y 29/55 and complement. Five patients with Burkitt's lymphoma were transplanted with purged marrow, demonstrating the clinical feasibility of the method. The pretransplant regimen included vincristine 2 mg/m2, adriamycin 60 mg/m2, four doses of cyclophosphamide 45 mg/kg and total body irradiation with 6 Gy. Tumour control appears to be better in patients with purged bone marrow as compared to an earlier patient group with unpurged marrow.

Adolescent↗

[Effect of two years of deferoxamine therapy on iron balance, ferritin, liver and heart in patients with thalassemia major].

The iron balance, the urinary excretion of iron between transfusions, the serum ferritin, the liver density, the size of the heart, the ECG and the echocardiogram of 14 children with thalassaemia major were assessed before and during or after 2 years of deferoxamine therapy (DF, 1 or 2 g/kg body weight/day according to age, by subcutaneous infusion on 5 days per week, 11 months per year). The mean iron balance decreased significantly (p less than 0.001) from 15.4 +/- 4 mg/kg body weight/month before DF to -7.1 +/- 9.4 mg/kg body weight/month in the first year of DF and increased to -2.5 +/- 6.5 mg/kg body weight/month during the second year of DF therapy. Despite administration of a constant dose of DF the urinary excretion of iron during the last days before transfusion was twice as high as during the first days after transfusion. The mean serum ferritin level fell from 6380 +/- 2600 ng/ml before DF to 5074 +/- 1600 ng/ml during the first and 4346 +/- 1900 ng/ml during the second year of DF therapy (p less than 0.05). There was no significant change in liver density or cardiac parameters.

Adolescent↗

Acute myelogenous leukaemia: maintenance chemotherapy after early consolidation treatment does not prolong survival.

To investigate the value of maintenance chemotherapy after early consolidation treatment, an attempt was made to induce remission in 162 previously untreated patients, age-range 7-65 years (median 43). The 74 patients who were still in remission after early consolidation treatment (given for 3-5 months) were assigned to either maintenance chemotherapy every 8 weeks for 2 years or to observation only. After a median observation period of 44 months there was no difference between the groups in duration of remission or survival. Surprisingly, patients above 40 survived longer after early consolidation (median 4 years) than did patients aged 40 and below (median 1.6 years, p = 0.0002).

Adolescent↗

Autologous bone marrow transplantation in the treatment of children and adolescents with advanced malignant tumors.

Nineteen patients with advanced malignant tumors, less than 20 years old were treated with intensive chemotherapy (vincristine 2 mg/m2 i.v. and adriamycin 60 mg/m2 i.v. on day - 7; cyclophosphamide 45 mg/kg i.v. on days -6 to -3), total body irradiation (TBI, 600 rads on day -1) and autologous bone marrow transplantation (ABMT, day 0). Prior to this procedure induction of complete or partial remission by conventional therapy was attempted. Ten patients had intra-abdominal non-Hodgkin's lymphoma (NHL); three, yolk sac tumor; three, Ewing's sarcoma; and three, neuroblastoma. The supportive care included reverse isolation, immunoglobulin 400 mg/kg i.v. q 2 weeks, cotrimoxazole per os, and cell support as needed. No correlation between the bone marrow dose and the time of hematological reconstitution could be established. Five of seven patients with intra-abdominal NHL stage III (transplanted in first remission) are surviving disease-free for 5+, 5+, 20+, 23+, and 35+ months after ABMT. None of three patients with intra-abdominal NHL stage IV is surviving (two of them were transplanted in second remission). One of three patients with yolk sac tumor is surviving disease-free for 27+ months. There are no survivors among the patients with Ewing's sarcoma and neuroblastoma. Only one of 19 patients was lost due to therapeutic complications, while 12 died due to tumor. Regarding treatment results for advanced intra-abdominal NHL, the procedure described here is comparable to the best conventional regimens. In vitro methods for tumor cell eradication in the collected bone marrow might further improve the results of ABMT.

Adolescent↗

Specific and nonspecific mechanisms of action of immunoglobulin G in therapy of idiopathic thrombocytopenic purpura (ITP).

The efficacy of IgG infusion therapy in ITP is now established even in cases resistant to other forms of therapy. However, the mechanism of action is still speculative. We assume that a correction of the elevated thrombocyte clearance is brought about at several levels. First, antibodies specific for an inciting antigen (and for which the patient is deficient) may remove free antigen and/or immune complexes which adhere to platelet surfaces, thereby rendering platelets less susceptible to clearance. Second, IgG may act nonspecifically by protecting the platelet surface from becoming covered with immune complexes. Third, monomeric IgG may display a nonspecific inhibitory effect at the level of the interaction of immunologically altered platelets with Fc receptors of mononuclear phagocytes. For the latter effect, good in vivo evidence exists. However, it must be born in mind that interaction of antibodies with Fc receptors is but one mechanisms for triggering adherence and endocytosis. A variety of other receptors and binding sites exists which may interact with immunologically altered thrombocytes. These may either trigger phagocytes on their own or facilitate the interaction of antibodies and Fc receptors. How IgG infusion influences such interactions remains to be determined.

Antibody Specificity↗

Interim evaluation of two cooperative studies assessing the effects of intravenous immunoglobulin (i.v. IgG) on childhood idiopathic thrombocytopenic purpura (ITP): I. Randomized study comparing i.v. IgG with oral corticosteroids in previously untreated acute ITP. II. Prospective study of i.v. IgG in acute and chronic ITP unresponsive to previous treatment.

Since in a pilot study i.v. IgG was shown to induce a rapid rise of thrombocytes in children with ITP two prospective multicenter ITP studies were started: one comparing i.v. IgG with oral corticosteroids in previously untreated acute ITP, the other investigating the response to i.v. IgG in pretreated acute or chronic ITP in childhood. In this report preliminary results of both studies are summarized. i.v. IgG treatment of acute and chronic ITP is at least as effective as corticosteroid therapy but is not associated with significant side effects. At least some patients with chronic ITP may benefit from i.v. IgG. Longer observation periods are required for further analysis.

Acute Disease↗

Hemophilia and thrombocytopenia in a patient with impaired cellular immunity. A case report.

ITP in hemophiliacs may produce severe bleeding complications. We here report on an eight-year-old boy suffering from severe hemophilia A, who developed ITP and an acquired impaired immune function similar to AIDS. Steroid therapy reverted the thrombocyte count to normal, however it had to be discontinued because of a severe Cushing syndrome. The thrombocytopenia also responded to IgG-therapy and the patient is treated with a long term schedule according to Imbach. It is of interest that the impaired T-helper/T-suppressor cell ratio (0.45) improved to a value of 1.0 after initiation of this therapeutic regimen. We conclude from our observation that i.v. immunoglobulin therapy is of particular value for the treatment of ITP in patients with impaired cellular immunity.

Acquired Immunodeficiency Syndrome↗

Haemophilia due to factor VIII inhibitors in a patient suffering from an autoimmune disease: treatment with intravenous immunoglobulin. A case report.

This paper describes a case of haemophilia due to factor VIII inhibitors occurring in a 13-year-old boy suffering from an autoimmune disease. The patient had autoantibodies to factor VIII. The haemophilia was controlled by vincristine and steroids, but this regimen had to be discontinued because of side effects, whereupon the haemophilia recurred. Treatment with intravenous immunoglobulin (IgG i.v.) produced a slow rise in factor VIII, and the factor VIII inhibitors disappeared. Although factor VIII activity was raised for only a few months and factor VIII inhibitors reappeared, immunoglobulin treatment was continued and the patient remained free of clinical symptoms. The mechanism of action of treatment with IgG is discussed.

Adolescent↗

The place of intravenous immunoglobulin (IgG i.v.) therapy in thrombocytopenia.

Acute ITP following infection in children has a high rate of spontaneous remission. Since the platelet count is not uncommonly profoundly depressed, ITP is associated with a mortality of around 1%. The aim of treatment in ITP is to prevent bleeding. As a rule, this can only be achieved by normalizing the platelet count. Intravenous immunoglobulin offers certain advantages over conventional steroid therapy. Moreover, two out of three patients with chronic ITP respond to IgG i.v. The characteristic features of ITP in pregnancy, thrombocytopenia in babies born to mother with ITP and neonatal isoimmune thrombocytopenia are discussed.

Adrenal Cortex Hormones↗

Intravenous immunoglobulin therapy: new aspects and outlook.

Experiences gathered while exploring the usefulness of intravenous immunoglobulin for children with idiopathic (immune) thrombocytopenic purpura (ITP) are reviewed in view of further investigations characterizing the effects of IgG i.v. in other immune diseases without detectable antibody deficiency. The most pertinent factors to be considered are i) the heterogeneity of an immune disease investigated; ii) the criteria used to evaluate the effects of the IgG therapy; iii) the IgG preparations used and i.v. dose-fractionation. Controlled, prospective clinical trials will be required to further explore the practical usefulness of IgG i.v.

Acute Disease↗

Intravenous immunoglobulin for idiopathic thrombocytopenic purpura (ITP) in childhood.

IgG-SRK (identical with Sandoglobulin) is a polyvalent IgG concentrate obtained by modified alcohol cryoprecipitation, including mild acidification at pH 4. This product was given in high doses intravenously for the treatment of six children with acute ITP, four children with intermittent ITP, and three children with severe chronic idiopathic thrombocytopenic purpura (ITP). An impressive initial response was observed in all patients, the extent of which may be of prognostic significance in acute ITP. Maintenance therapy was required in two of six patients with acute ITP, in three out of four patients with intermittent ITP, and in all of the patients with severe chronic ITP. In the cases of severe chronic ITP, the disease could not be adequately controlled over long periods of time, but bleeding episodes subsided or became considerably less frequent. Although little is known of the effects of IgG-SRK, possible mechanisms were discussed. It is emphasized that a new model has been discovered to study the interrelations between structure and function of human immunoglobulin molecules.

Acute Disease↗

Differentiation and cytokinetic analyses of normal and neoplastic lymphoid cells in B and T cell malignancies of childhood.

The labelling index (LI) of untreated B cell non-Hodgkin's lymphoma (B NHL) in children was significantly higher (P less than 0.002) than the LI of untreated T cell malignancies (median LI 27.7% and 10.3%, respectively). In B NHL abdominal tumour material showed a significantly higher in vitro incorporation of tritiated thymidine (3H-dT) than extra-abdominal tumour material (P less than 0.01). Sequential immunological, cytochemical and cytokinetic studies revealed tumour cells in up to three marker-defined subpopulations of lymphoid cells. In all 14 patients examined the LI of E-Ia+sIgM+ cells was higher than the LI of E+Ia+/-sIgM- cells; in all eight patients with Ia+ and Ia- tumour cells the former had a higher LI than the latter (P less than 0.002). In all T cell neoplasia (T ALL/NHL) investigated malignant cells were found in two of the three marker-defined subsets of lymphoid cells. In 10/13 patients the E-rosette positive blast cells had a higher LI than the E-rosette negative T blast cells. For the small group of patients with T cell malignancies no significant difference in the overall LI between OKT9+ stage I (early thymocyte) and OKT9- stage II (cortical thymocyte) neoplasias could be found. However, within the malignant clone of a T cell malignancy the expression of the OKT9 (transferrin receptor) but not the cortical thymocyte (HTA-1) antigen was related to the in vitro 3H-dT incorporation.

Adolescent↗

Electroencephalographic findings in children treated with cytotoxic agents.

106 EEG investigations were carried out in 17 children with various types of neoplastic disease without cerebral involvement during one or more courses of treatment with cytotoxic agents. EEGs were recorded before and 24 h after administration of the drugs. A transient slowing of the dominant frequency in the alpha-band by about 1 c/s and a decrease in the relative power of alpha-activity by 20-30% was observed in only 4 patients. These children did not receive the same antineoplastic treatment. 1 patient received very high dose methotrexate, 2 patients received vincristine combined with other cytotoxic agents, and the other patient received L-asparaginase. It is suggested that EEG changes in patients receiving intravenous cytotoxic treatment usually occur only where there is a preexisting impairment of the blood-cerebrospinal fluid barrier or the blood-brain barrier.

Adolescent↗

Expression of HLA-DR antigens and cell proliferation in acute lymphoblastic leukemia of children.

Non-T, non-B acute lymphoblastic leukemia (ALL) in children can be further subdivided into common, null/undifferentiated and pre-B ALL. The overall labelling indices (LI) showed comparable values for these 3 subtypes of ALL. By sequential immunological, cytochemical and cytokinetic studies on single bone marrow cells, combined with morphological evaluation, blast cells could be attributed to the compartments of E-Ia+sIgM- and E-Ia-sIgM- cells, in pre-B/B ALL also to the compartment of E-Ia+sIgM+ cells. In all 30 patients investigated, the LI of Ia+ blast cells was higher than the LI of Ia- blast cells (p less than 0.001). However, no correlation between the percentage of Ia+ blast cells and the overall LI could be found in these patients (r = 0.284; p greater than 0.1).

Antibodies, Monoclonal↗

Varicella and herpes zoster in immunosuppressed children: preliminary results of treatment with intravenous immunoglobulin.

Seven immunosuppressed children with varicella and two with herpes zoster were treated with large intravenous doses of polyvalent, intact immunoglobulin (IgG i.v.). In all patients the treatment was effective for controlling fever and skin lesions and for preventing progression and complications, even if this therapy was started late and/or if the patient was severely lymphopenic . More IgG was needed to control disseminated than less advanced varicella. No untoward effects of IgG therapy were observed. The preliminary results suggest that in future trials i.v. IgG should be used for comparison with antiviral agents.

Adolescent↗

[High-dose immunoglobulin infusions in idiopathic thrombopenic purpura].

In childhood approximately 90% of all idiopathic thrombocytopenic purpuras (ITP) are acute while in adults the majority is chronic (6 months duration). 0,5 - 1% of the children with ITP die. Conventional treatment comprises corticosteroids and, for chronic ITP, splenectomy and/or cytostatic immunosuppression. Inspired by the disappearance, during substitution, of concomitant ITP in 2 agammaglobulinemic boys, 13 children with ITP (3 chronic, 4 intermittent, 6 acute) were treated with high-dose intravenous immunoglobulin SRK. All responded favorably but one boy with chronic ITP became resistant after 11 months of infusions. F(ab')2 fragments are inactive. High doses of immunoglobulin could block Fc receptors of macrophages. They could also facilitate the formation and elimination of immune complexes and, indirectly, prevent the accumulation of platelet-associated immunoglobulin.

Blood Platelets↗