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Biomedical subjects

A Fateh-Moghadam

Publications and source records attributed to A Fateh-Moghadam.

At least 55 records · Page 3Linked to original sources

[The diagnosis of multiple myeloma].

The diagnosis of multiple myeloma (MM) is often made in an advanced phase when using the established criteria. Derived from the modern diagnostic procedures used in malignant lymphomas, an alternative diagnostic strategy in MM is proposed. The prognostic value of a histologic classification of MM has been demonstrated, based on bone marrow biopsies of 577 myeloma patients. Furthermore, the infiltration volume in the biopsy proved to be an important prognostic parameter and complements the used clinical staging system. The different possibilities of a reliable follow-up of myeloma patients are shown.

Blood Proteins↗

Thymectomy in myasthenia with pure ocular symptoms.

Eighteen patients with exclusively ocular symptoms of myasthenia were thymectomised. Suspected thymoma, resistance to pyridostigmine therapy or relapse following immunosuppressive therapy were taken as indications for surgery. The mean preoperative observation period before operation was 40 months, and after operation was 26 months. There was no operative or postoperative morbidity or mortality. Histological thymic abnormalities were found in all patients (in one case, thymoma; in four, persistent thymus; in 13, thymic hyperplasia). The histological abnormalities were identical to those found in generalised myasthenia. This included the distribution of T-cell subtypes as identified by use of monoclonal antibodies. The severity of ocular symptoms was rated using a score developed for this purpose. The score progressively declined after surgery to an average of 70% of its initial amount in 80% of patients. Full remission occurred in three cases. No patient developed generalized myasthenia. Antibody titres against acetylcholine receptors if elevated preoperatively also dropped following surgery, with one exception. Clear criteria for the expected therapeutic success of thymectomy could not be identified. Based on our results, and on the assumed significance of the thymus gland for pathogenesis, thymectomy should be considered in patients with pure ocular symptoms.

Adult↗

[Immunophenotyping of lymphocyte subpopulations using monoclonal antibodies in an analytical flow cytometer: evaluation of the method and reference values].

Analytical flow cytometers which are easy to operate, and monoclonal antibodies specific for cell surface determinants of lymphocytes, offer a simple and rapid method for the identification of the immunological phenotype of lymphocyte subsets. We investigated mononuclear cells isolated from EDTA-blood bv density gradient centrifugation. The intraassay precision (n = 12) of the determination by means of monoclonal antibodies directed against T-cells (Leu 4), T-helper/inducer-cells (Leu 3 a, b), T-suppressor/cytotoxic cells (Leu 2 a) and cells of the 'NK'-phenotype (Leu 7) varied between 2.2 and 7.9%. Studies using the subset markers Leu 2a and Leu 3a, b conjugated either to fluorescein isothiocyanate (FITC) or to phycoerythrin (PE) showed comparable results for both subsets. Dual immunofluorescent analysis using two different antibodies conjugated to contrasting fluorochromes resulted in slightly higher fractions of T-helper/inducer-cells (Leu 3a, b-FITC: a = 0.97, b = 3.18, r = 0.98) and T-suppressor/cytotoxic cells (Leu 2 a-PE: a = 0.99, b = 2.22, r = 0.97) compared with single immunofluorescent analysis. We found no constant association to explain this statistically significant discrepancy (p less than or equal to 0.0002). The investigation of 100 controls established the following reference values for the fraction of lymphocyte subsets (median, 95%-interval): T-cells 0.75 (0.57-0.87), T-helper/inducer-cells 0.47 (0.34-0.63), T-suppressor/cytotoxic cells 0.26 (0.15-0.42), 'NK'-cells 0.16 (0.04-0.34). The corresponding absolute numbers of cells are: T-cells 1.300 (0.730-2.240), T-helper/inducer-cells 0.820 (0.44-1.540), T-suppressor/cytotoxic cells 0.450 (0.190-0.915), 'NK'-cells 0.300 (0.060-0.670).

Adult↗

[Antibody-controlled cytostatic therapy of malignant thymoma with concomitant myasthenia gravis].

In a 46-year-old female patient with malignant thymoma and concomitant myasthenia gravis relapse with gravitational metastases occurred 6 1/2 years after the first operation. Metastases could be removed surgically only partially and were subsequently irradiated with 50 Gy. After 3 1/2 years renewed metastatic growth occurred. Until then the concomitant myasthenia had been stable during treatment with pyridostigmine and azathioprin and intermittent prednisone; acetylcholine receptor antibody titres had remained largely stable. Combined cytostatic treatment with vincristine, cyclophosphamide, prednisone and doxorubicin or cisplatin led to regression of metastases during the observation period of 1 1/2 years and at the same time to stabilisation of the myasthenia. Acetylcholine receptor antibody titres decreased and this was roughly paralleled by clinical improvement. Whereas there is no obvious correlation of antibodies against acetylcholine-receptor protein and tendency of tumour growth there is good agreement with the course of the accompanying myasthenia.

Acetylcholine↗

[Correlation of acetylcholine receptor antibodies and clinical severity of myasthenia gravis in combined immunosuppressive therapy].

The correlation between the severity of symptoms in myasthenia gravis (score) and the level of acetylcholine receptor-antibodies (ACHR-Ab) was studied in 24 patients treated with immunosuppressive therapy. This correlation was significant in every case regardless of whether or not thymectomy was performed in addition. It was demonstrated by means of a long-term follow up study, that a change in ACHR-Ab preceeds the corresponding change in score by 2-4 months in 80% of our patients. Measurements of ACHR-Ab ease the management of the therapy with immunosuppressants and make it safer. This is particularly true prior to and after termination of the treatment. A change in ACHR-Ab level by more than 20% indicates a change in score.

Adult↗

[High-dose immunoglobulin therapy in autoimmune diseases].

High-dose intravenous immunoglobulin is being used increasingly as a new therapeutic approach towards various autoimmune diseases, yielding encouraging results predominantly in idiopathic thrombocytopenic purpura (ITP). A marked initial increase of the platelet count has been observed in the majority of patients with acute and chronic ITP alike after high-dose immunoglobulin. In contrast to acute ITP, where full or partial remissions have been achieved in nearly all cases, long-term results reached in chronic ITP, where lasting increases of platelet counts have been observed predominantly in splenectomized patients, have proved to be less favourable. Correspondingly, several cases of other forms of autoimmune thrombocytopenia and neutropenia successfully treated by high-dose immunoglobulin have been reported. We contribute our own experience in 4 patients with myasthenia gravis, where administration of 7S-immunoglobulin but not of 5S-immunoglobulin was followed by both a clinical remission as well as a decrease of specific autoantibody concentration. While several mechanisms of action of high-dose immunoglobulin are discussed, there is evidence for an immunosuppressive effect and for the Fc-fragment dependency of the therapeutic efficacy. Although high-dose immunoglobulin has proved to be a promising therapeutic option especially in ITP, indications will have to be defined yet by further investigations and may be restricted to emergency and refractory cases.

Arthritis, Rheumatoid↗

[Computer-assisted findings on protein electrophoresis on cellulose acetate film].

Until a short time ago efficient computer assisted reporting of electrophoretograms was not possible owing to the lack of appropriate technology. By integrating a fully mechanized electrophoresis system into the laboratory data processing system of a centralized institute of clinical chemistry, the separation and the interpretation of results can be performed for 300 samples per day. The interpretation is based upon available patient data (specified clinical diagnoses, previous results), calculated fractions and analysis of the electrophoretic curve in the area of albumin and the beta- and gamma-globulin fraction. In this way it is possible to classify hereditary bisalbuminaemias and to detect transient bisalbuminaemias and monoclonal gammopathies. Diagnostic indications of specific dysproteinaemias and defect proteinaemias are printed on the report form if individual serum protein fractions and the total protein content are changed specifically. The results of the different electrophoretic fractions, the total protein and a set of possible alterations of the curve are numerically coded according to the scaled biochemical ranges in five definite sections or to a decision matrix (alteration 'given' or 'not given'), respectively. The composed 'result patterns' are matched with preassigned 'reference patterns' stored in the computer file. The procedure is efficient and adaptable to other areas of analysis.

Albumins↗

[Comparative protein analytic studies of various intravenous 7S-immunoglobulin preparations].

Seven different commercial intravenous 7S-immunoglobulin preparations have been examined by electrophoresis, immunoelectrophoresis, quantitative determination of immunoglobulins and other proteins, gel chromatography and analytical ultracentrifugation. No significant difference concerning IgG and monomeric immunoglobulin concentrations was observed. The content of IgM, dimers and polymers showed slight, that of IgA considerable differences. All immunoglobulin preparations comply with the European Pharmacopoea requirements. The rate of adverse reactions should be equally low due to similar dimer and polymer contents. IgA-free preparations are considered to be more suitable in primary hypogammaglobulinaemia whereas IgA-containing preparations could be of benefit in acquired hypogammaglobulinaemia. While the presence of an intact immunoglobulin molecule is thought to be essential for its full therapeutic efficacy, the influence of the preparation method is still in debate.

Blood Protein Electrophoresis↗

[Diagnosis of central nervous system diseases. Multivariate analysis of the serum-cerebrospinal fluid- protein relation].

In a population comprising 197 patients serum and CSF proteins were assayed using the radial immunodiffusion technique devised by Mancini. Multiple discriminant analysis was applied to investigate whether the measured CSF/serum protein relations and their ratios could be regarded as an indicator of specific neurologic diseases. One significant finding was that the slope angle alpha of the regression line between the serum/CSF relation and molecular weight may represent an important indicative parameter. A small angle is suggestive of enhanced permeability of the blood-brain barrier, a large angle of a correspondingly lowered permeability. Further, the analyses demonstrated that the combined use several predictors can markedly improve differential diagnosis. The study also demonstrates the potential of a statistical analytic technique that is still rarely applied in medicine.

Analysis of Variance↗

Myasthenia gravis: overlap with 'polyendocrine' autoimmunity.

81 patients with spontaneously acquired myasthenia gravis (MG) were investigated for the presence of autoimmune (AI) diseases and their sera were tested for a range of organ-specific autoantibodies. 77 of the patients were HLA-phenotyped. Antibody titres to acetylcholine receptors (AChR) were higher in non-thymomatous patients who possessed HLA-B8 (p less than 0.05) and/or -DR3 (p less than 0.05) as compared to patients lacking these HLA antigens. 3 out of 20 (15%) patients with ocular MG, 7/23 (30%) with generalized MG of early onset, 11/23 (48%) generalized MG of late onset and 5/14 (35%) patients with thymoma had either overt AI diseases or significant titres of organ-specific autoantibodies suggesting subclinical AI disease. In ocular MG, low titres and an infrequent finding of antibodies to AChR (32%) as well as the low prevalence of associated autoantibodies and AI diseases indicate that this subgroup of MG consists of patients with restricted AI reactivity. HLA-B8 and -DR3 were present in all the patients with associated AI disorders in the young onset group but in none of the patients with old age of onset. In the young group, 6 out of 7 patients with associated AI conditions were women whereas the sex ratio was about equal in the older cases in both, patients with and without associated AI diseases or autoantibodies. We conclude from these observations that ageing provides conditions that allow the breakdown of self tolerance. The simultaneous presence of HLA B8, DR3 and female sex provide important additional factors for early expression of MG.

Adult↗

[Immunogenetics of myasthenia gravis. Significance of HLA-, complement and Cm gene systems for clinical and immunologic parameters].

In 82 non-related patients with myasthenia gravis the following immunogenetic marker systems were investigated: HLA-A, -B, -C, -DR antigens, complement polymorphisms for Bf, C3 and C4 as well as immunoglobulin allotypes G1m, G3m and Km. In 78 patients the level of circulating acetylcholin receptor autoantibody was measured. The HLA antigens showed no significant differences in frequency when compared with healthy controls. This was also true for the HLA-bound Bf and C4 polymorphism, the non-HLA-bound C3 polymorphism and the immunoglobulin allotypes. A significant (P less than 0.005) increase in heterozygote frequency of 39.7% in the Gm allotype combination G1m (1), (17); (3) when compared with an expected frequency as calculated from the gene frequency of 19.8% was found. HLA-B8 and/or HLA-DR3 positive myasthenia gravis patients showed a significantly (P less than 0.025 and less than 0.005) earlier average onset of the disease whereas in HLA-DR2 positive patients the average onset was later (P less than 0.05). The same HLA antigens correlated with quantitative differences in the acetylcholine receptor autoantibodies: HLA-B8 and/or -DR3 positive patients had on average higher antibody levels than HLA-B8 or -DR3-negative patients. The difference for HLA-DR3 was statistically significant (P less than 0.05). On the other hand patients with HLA-DR2 antigens had significantly lower antibody levels (P less than 0.025). Increased mean antibody levels were also seen in G1m(1), (17) allotype (P less than 0.005) and G3m(21) (P less than 0.05). As the HLA antigens and Gm allotype genes are situated on different chromosomes (C6 and C14) two distinct gene regions are identified in myasthenia gravis. These are associated with quantitative differences in acetylcholine receptor antibody titres.

Autoantibodies↗

Multivariate analysis of the serum-cerebrospinal fluid-protein-relation for the diagnosis of neurological diseases of the central nervous systems.

In a population comprising 197 patients, serum and CSF proteins were assayed using the radial immunodiffusion technique devised by Mancini. Multiple discriminants analysis was applied to investigate whether the measured CSF/serum protein relations and their ratios could be regarded as an indicator of specific neurological diseases. One significant finding was that the slope angle alpha of the regression line between the serum/CSF relation and molecular weight may represent an important indicative parameter. A small angle is suggestive of enhanced permeability of the BBB, a large angle of a correspondingly lowered permeability. Further, the analyses demonstrated that the combined use of several predictors can markedly improve differential diagnosis. The study also demonstrates the potential of a statistical analytic technique that is still rarely applied in medicine.

Blood Proteins↗

Bone marrow histology in Waldenström's macroglobulinaemia. Clinical relevance of subtype recognition.

Bone marrow biopsies of 137 patients with Waldenström's macroglobulinaemia (WM), 26 with non-secretory immunocytoma and 32 with benign monoclonal gammopathy were processed for histologic evaluation. Bone marrow involvement was found in 110 (80%) initially, and in 24 (18%) in sequential biopsies. 3 types were distinguished: lymphoplasmacytoid (47%), lymphoplasmacytic (42%) and polymorphous (11%) with median survivals of 74, 25 and 12 months, respectively. When grouped according to the tumour cell mass in the biopsies, the median survivals were 55, 21 and 8 months for less than 20 vol%, 20-50 vol% and greater than 50 vol% respectively; in each subtype, the tumour cell mass correlated with the disease progression. 6 clinical variables were also found prognostically significant. These results demonstrate that (i) 98% of patients with WM have bone marrow involvement; (ii) the lymph node sub-classification is applicable to the bone marrow and has both clinical and prognostic significance; (iii) patients may be staged according to the tumour cell burden in the bone marrow biopsy.

Adult↗

Myasthenia gravis: long-term correlation of binding and bungarotoxin blocking antibodies against acetylcholine receptors with changes in disease severity.

Sixty patients with myasthenia gravis were examined prospectively by measuring serial titers of antibodies against human acetylcholine receptor, and these were correlated with a quantitative clinical score. Serial titers of antibodies detected by the standard immunoprecipitation assay (binding antibodies) correlated with the clinical score in most patients. Antibodies blocking the binding of alpha-bungarotoxin to receptors (blocking antibodies) were detected in 29 patients. Serial blocking antibody titers correlated with changes in muscle weakness less often than binding antibody titers. Titers of both classes of antibodies often followed a divergent course, suggesting that the autoimmune B-cell clones that formed these classes of antibodies may have been activated asynchronously.

Acetylcholine↗

Bone marrow histology in myeloma: its importance in diagnosis, prognosis, classification and staging.

A study has been made of 420 bone marrow biopsies from patients with multiple myeloma (220), idiopathic monoclonal gammapathy (50), reactive plasmacytosis (42) and solitary plasmacytoma (22). Histology and immunohistological parameters were more reliable than cytology in distinguishing a reactive from a neoplastic plasmacytosis. Histological variables were correlated with the clinical features of the patients to determine the factors which were of value in predicting prognosis. Plasma cell maturity and the extent of infiltration in the biopsy by myeloma cells proved to be highly significant in predicting the duration of survival. On the basis of these criteria multiple myeloma was classified into two types: plasmacytic of low-grade malignancy and plasmablastic of high-grade malignancy; and into three stages which accurately reflected the progression of the disease. We conclude that a bone biopsy provides useful information for the diagnosis, classification and staging of patients with multiple myeloma.

Bone Marrow↗