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Biomedical subjects

P Imbach

Publications and source records attributed to P Imbach.

At least 55 records · Page 3Linked to original sources
PubMed1990

High-dose intravenous immunoglobulins in HIV-1-infected adults with AIDS-related complex and Walter-Reed 5.

The influence of high-dose intravenous immunoglobulins (HD-IVIG) on the clinical status and T4 cell count of adults with AIDS-related complex (ARC) and Walter-Reed 5 (WR5) was evaluated in a randomized double-blind longitudinal study. Inclusion criteria were: (1) T4 cells less than 400/microliters and (2a) oral thrush or cutaneous anergy or (2b) two clinical ARC criteria (fever, diarrhea, weight loss, fatigue, night sweats). Thirty patients [28 males, 2 females, median age 41 (24-64) years] with ARC (n = 8), WR5 (n = 12) and both (n = 10) were stratified according to their T4 cell count (greater than or equal to vs. less than 300/microliters). Fifteen patients received 0.4 g/kg body weight IVIG and 15 placebo (albumin 0.03%) every other week for 26 weeks with follow-up for another 26 weeks. The clinical status was defined as a score consisting of fever, diarrhea, night sweats, fatigue, weight loss, oral candidiasis and mucosal or cutaneous herpes simplex. Clinical examination and routine laboratory assessments were performed before initiation of the study and before each administration, lymphocyte phenotyping every 4 weeks and cutaneous reaction, serology and lymphocyte stimulation every 12 weeks. Both groups were comparable in initial clinical symptoms and laboratory values. Seven patients developed AIDS (treatment group: 3, placebo group: 4), 1 patient died by homicide. After 26 weeks, the clinical score (particularly fatigue and fever) was significantly improved in the treatment group, while the T4 cell count and other clinical and immunological parameters remained unaltered. This limited effect was still evident at termination of the study after 52 weeks. In conclusion, HD-IVIG can improve the clinical status of patients with advanced HIV-1 infection without obviously correcting the underlying impaired cellular immunity. The substitution of intact antibodies in the state of functional hypogammaglobulinemia is suggested as possible therapeutic mechanism.

AIDS-Related Complex↗
PubMed1989

Prevention of chronic ITP?

The treatment of childhood ITP with IVIG has been widely used in acute or in previously treatment-dependent, chronic forms of the disease. We discuss propositions of a prospective multicenter study to evaluate the efficacy of IVIG to prevent the development of chronic ITP in childhood. The problems of such a study, i.e. evaluation criteria, number (about 10% of patients with acute ITP will develop the chronic form) and related topics are discussed.

Child↗
PubMed1989

Chronic immune thrombocytopenic purpura--immunological analyses of a patient pre- and post-HIV seroconversion.

A seven year follow-up of immune parameters is reported for a patient with chronic immune thrombocytopenic purpura (ITP) pre and post human immunodeficiency virus (HIV) seroconversion. Therapies such as intravenous IgG, prednisone, vincristine, or Ciclosporin A had no clear-cut beneficial effect on platelet counts. A long-term normalization of platelet counts was achieved by splenectomy. At splenectomy the patient was seropositive for HIV, most likely transmitted by blood products received half a year prior to laparatomy. Mean plasma levels of the second component of complement, C2, were half of the normal values prior to and within the lowest normal range post HIV seroconversion. Nevertheless, the T cell-dependent B cell response to HIV, which is dependent on the activation of C3 via the classical pathway of complement, was normal: Western blot analysis of total IgG and of IgG subclass responses to individual HIV antigens proved to be unimpaired.

Antigen-Antibody Complex↗
PubMed1989

Idiopathic thrombocytopenic purpura (ITP): immunomodulation by intravenous immunoglobulin (IVIg).

ITP is a destructive thrombocytopenia. Platelets are coated with antibodies and these opsonized platelets are rapidly removed by phagocytes. On the other hand, therapeutic application of antibody concentrates (IVIg) rapidly raise platelet counts, and in some patients, sustained platelet recovery has been observed. The mechanism of action of IVIg is far from being clear. Several possible mechanism of action of IVIg treatment have been described. The immediate effect of IVIg seems to be a decrease in (unspecific) Fc mediated mononuclear phagocytosis, the long term effect might be a change in the complex network of the regulatory function of the immune response. Both types of interactions seem to play a keyrole in the immunomodulation. The various possible modes of actions evoke investigation of IVIg in a wide range of diseases with similar ineffective immune response. Controlled clinical studies have to be done to prove or disapprove the use of IVIg in other indications.

Autoimmune Diseases↗
PubMed1989

[New indications for the use of immunoglobulins].

In the present review we discuss new clinical indications for IVIG therapy. Presently, clinical studies are under way to examine the effect of IVIG in uncommon diseases such as intractable epilepsy in children, myastenia gravis and necrotizing hemorrhagic enteritis. These considerable efforts in clinical research will most likely lead to new established indications for the use of IVIG.

Autoimmune Diseases↗
PubMed1988

Intravenous immune globulin in symptomatic paediatric human immunodeficiency virus infection.

Seven paediatric patients with symptomatic human immunodeficiency virus (HIV) infection were prospectively studied for 6-24 months after the start of intravenous immune globulin (IVIG) therapy. There was substantial clinical benefit during IVIG treatment with marked reduction of febrile and infectious episodes, normalization of physical and psychomotor development, and absence of mortality. The immunologic monitoring revealed some discrete objective improvements. The results of this study favourably compare to previous reports. It is concluded that IVIG should be standard therapy for symptomatic childhood HIV infection.

AIDS-Related Complex↗
PubMed1988

Intravenous immunoglobulin (i.v. IgG) for previously treated acute or for chronic idiopathic thrombocytopenic purpura (ITP) in childhood: a prospective multicenter study.

In a prospective multicenter study 42 thrombocytopenic (less than 30 X 10(9) platelets/l) children with chronic idiopathic thrombocytopenic purpura (ITP) or with acute ITP, dependent on or refractory to corticosteroids, were given 0.4 g i.v. IgG/kg body weight/day on 5 consecutive days and thereafter once a week if the platelet count fell to less than 20 X 10(9)/l or if the patient bled. After the initial 5 days of i.v. IgG the platelets rose within a mean of 7-8 days to greater than 30 X 10(9)/l in all and to greater than 150 X 10(9)/l in 33 of 42 patients (79%). After a mean observation time of 26.6 months 26 of 42 patients (62%) showed a satisfactory long-term effect, i.e. no need for treatment for at least 6 months without bleeding and with no platelet counts below 20 X 10(9)/l. No difference in response rate was found between children with chronic and those with previously treated acute ITP. These results indicate that i.v. IgG could be used to control emergency situations, e.g. to stop bleeding or to prepare a patient for surgery. I.v. IgG also represents a good alternative to treatment modalities, such as splenectomy and/or the administration of cytostatic immunosuppressants with potentially serious side effects. In addition to the expected transient rise in serum IgG levels, i.v. IgG induced a more prolonged elevation of serum IgM. Platelet associated IgG, elevated before therapy, was correlated with the clinical long-term outcome.

Acute Disease↗
PubMed1988

Intravenous immunoglobulin therapy for idiopathic thrombocytopenic purpura and other immune-related disorders: review and update of our experiences.

Idiopathic thrombocytopenic purpura (ITP) is a disorder characterized by a destructive thrombocytopenia. Since the demonstration of a humoral antiplatelet factor which causes a transient ITP when given to healthy volunteers, ITP has been thought of as an autoimmune disease. The target antigen seems to be heterogeneous; it is either a primary platelet membrane autoantigen or a secondary autoantigen absorbed on the platelet. The former was recently confirmed by the observation that serum and platelet eluates of patients with ITP bind to normal platelets, but not to Glanzmann's thrombasthenic platelets which are deficient in glycoproteins IIb and IIIa. The heterogeneity of ITP is also reflected in the difference in response to immunoglobulin prepared for intravenous administration (IVIG) treatment. In our multicenter studies for severe ITP (less than 30 X 10(9)/liter platelet count) in children, we observed the existence of at least two subgroups of ITP, namely rapid responders (greater than or equal to 30 X 10(9)/liter platelet at 72 hours after the start of IVIG) and slow responders (less than 30 X 10(9)/liter platelet counts at 72 hours). Rapid responders mostly showed a permanent increase of their platelet counts while slow responders often had a transient platelet increase. Slow responding children were therefore comparable with adults with ITP. Because the adult type of ITP occurs often in young women, fetal risk must frequently be addressed. The situation of neonatal ITP reflects both the antigenic and therapeutic heterogeneity of ITP. The severity of the disease probably depends on the character of the antigen and its related autoantibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1988

Proliferation of lymphoid precursor cells in the bone marrow of patients with various disorders of the immune system.

In the human bone marrow the nuclear enzyme terminal deoxynucleotidyl transferase (TdT) is expressed by cells during early stages of lymphocyte differentiation. In order to investigate a possible regulation of lymphopoiesis at this level of differentiation, the relative frequency and the in vitro 3H-thymidine labeling index (3HdT-LI) of TdT-positive bone marrow cells were assessed in patients with different functional activities of the immune system. TdT-positive lymphoid precursor cells could be detected in the bone marrow of all children investigated, including six patients with various forms of immunodeficiency. Neither a transient hyperfunction of the immune system during the immunological rebound after cessation of long-term chemotherapy for acute lymphoblastic leukemia, nor a congenital or acquired hypofunction of the immune system had any detectable influence on the invariably high in vitro 3HdT-LI of TdT-positive bone marrow cells, a phenomenon possibly related to an autonomous and high turnover of this precursor cell compartment in the human bone marrow.

Adolescent↗
PubMed1987

Long-term results of two Swiss AML studies.

The Swiss group for clinical cancer research (SAKK) completed two first line protocols for the treatment of acute myelogenous leukemia (AML). In the first protocol (SAKK AML 74, from August 1974 to April 1977; 107 patients) the effectiveness of immunization with viral oncolysate during maintenance treatment was tested. After successful induction treatment, the patients were randomized in two groups: Group A: monthly maintenance chemotherapy for 2 years and group A+IT, which received the same maintenance chemotherapy regimen plus, on day 15, injection of viral oncolysate. Of the 107 patients, 57 (53%) achieved complete remission, 29 then being randomized to group A, 28 to group A+IT. As of August 1984, there is no statistical difference between the survival times of the two groups (p = 0.288). Ten years after the start of the study there is still no clear plateau of the survival curve. Nine percent of all patients (18% of the remission patients) are alive today. With the treatment of the mid-seventies, therefore, the cure of a patient suffering from AML was a rare event. The second protocol (SAKK AML 77, from April 1977 to April 1982; 162 patients) was designed to evaluate the usefulness of a prolonged maintenance treatment after early consolidation. The 74 patients who were still in remission after early consolidation treatment were assigned to either maintenance chemotherapy or to observation only. At 3.5 years after the last patient's entry there was no difference between the groups in duration of survival (p = 0.332).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Reactivity of monoclonal antibodies LAU-A1 and anti-Y 29/55 in T and B cell malignancies of children: correlation with immunological markers and clinical data.

The monoclonal anti-pan-T cell antibody LAU-A1 stained neoplastic T cells arrested at different levels of maturation from all 21 children with T cell malignancies examined. Particularly in 7 patients with immature T cell neoplasia staining for LAU-A1 facilitated the recognition of a T cell origin of the malignant cells. Only 40% of these immature T cell malignancies were associated with an anterior mediastinal mass. A subdivision of T cell neoplasia into 4 differentiation-related subgroups did not permit to make predictions regarding the patients' survival. Despite the rather uniform clinical presentation the immunological phenotypes of tumor cells in 14 children with B cell non-Hodgkin's lymphoma (B NHL) were heterogeneous. Tumor cells lacked surface immunoglobulins (2 patients), expressed IgM only (7 patients), IgM and IgD (3 patients) or IgM, IgD and IgA (2 patients). Regardless of surface immunoglobulin expression anti-Y 29/55 stained practically all recognizable tumor cells of all B NHL examined. No correlation was found between the number of heavy-chain isotypes expressed on tumor cells and the survival of the patients. The only long-term survivors were 3 children transplanted with autologous bone marrow which had been purged in vitro with anti-Y 29/55 and complement.

Adolescent↗
PubMed1985

[Clinical characteristics of immature T-type (negative E-rosette) acute lymphoblastic leukemia detected by LAU-A1 monoclonal antibody].

Immature T-ALL is a newly defined subgroup of ALL in which the blasts lack the receptor for sheep erythrocytes (ER) and the usual T-cell markers, but express the 40 kDa pan-T surface antigen recognized by our monoclonal antibody LAU-A1. Patients with immature T-ALL represent 10% of all cases of adult ALL. Leukocyte counts are lower and spleen, liver and lymph node enlargement is less prominent, but mediastinal enlargement is more frequent than in mature (ER-positive) T-ALL. 7 patients with immature T-ALL (median age 42 years, range 13-73) were treated with intensified chemotherapy regimens, and only one 47-year-old female entered a short-lived complete remission. The overall survival of our patients was poor (median 7.5 months, with only one patient surviving at 15 months) and seemed not to be influenced by age. Our study indicates that immature T-ALL can only be accurately identified by the use of monoclonal antibodies recognizing the 40 kDa pan-T antigen, and that immature T-ALL is a separate disease entity typified by a poor prognosis.

Adolescent↗
PubMed1985

[Autologous bone marrow transplantation--clinical experience in Berne].

Autologous bone marrow transplantation was performed in 28 pediatric and adult patients with various neoplasias. Long-term remissions were obtained in one patient with yolk sac tumor and in 9 patients with B-cell non-Hodgkin's lymphoma. The relapse rate was decreased in patients receiving in-vitro decontaminated marrow (anti-Y 29/55 and complement).

Adolescent↗
PubMed1985

Intravenous immunoglobulin versus oral corticosteroids in acute immune thrombocytopenic purpura in childhood.

In a randomised, multicentre study intravenous IgG was compared with oral corticosteroids in 108 children with untreated acute immune thrombocytopenic purpura. IgG was an efficient treatment with no severe untoward reactions. The effects of corticosteroids and IgG were identical for rapid responders, who accounted for 62% of all patients. In contrast, patients requiring more than initial treatment responded better if randomised to IgG. The serum IgG level increased two-fold after IgG. A significant rise in IgM levels was observed after both IgG and corticosteroids. The platelet-associated IgG index was high in 75% of all patients. No significant differences between the two treatment groups were found, but rapid responders had a smaller mean initial platelet-associated IgG index which returned more rapidly and more permanently to normal than that of slow responders.

Acute Disease↗
PubMed1985

Treatment of acute idiopathic thrombocytopenia of childhood with intravenous infusions of gammaglobulin.

Gammaglobulin treatment was given at a dose of 1 gm/kg/day intravenously in 29 patients with acute idiopathic thrombocytopenic purpura: 15 previously untreated, 10 resistant to steroids, and four who were steroid dependent. The average platelet increase in 24 hours was greater than 50,000/microliter; the average peak platelet count was 194,000/microliter. Eighteen of 25 patients required only one infusion; 10 of these 18 never required any additional (maintenance) therapy. Outcome in previously untreated and steroid-resistant patients was identical; however, previously untreated patients required only 1.8 gm/kg total dose of gammaglobulin, whereas steroid-resistant patients received 3.9 gm/kg. Only one steroid-dependent child of the 29 patients still requires maintenance therapy, at 6-week intervals. Toxicity was minimal. Cost was minimized by not admitting patients and by giving treatment in one visit, rather than five.

Acute Disease↗
PubMed1985

A multicenter European trial of intravenous immune globulin in immune thrombocytopenic purpura in childhood.

Since a pilot study of intravenous immune globulin showed it to induce a rapid rise of thrombocytes in immune thrombocytopenia purpura (ITP) in childhood, a randomized study was started for acute, untreated ITP and a prospective study for acute and chronic, pretreated ITP in children. The results of the pilot study and preliminary data of the ongoing studies are presented. Although little is known of the effects of intravenous immune globulin, possible mechanisms of action are discussed.

Acute Disease↗