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Biomedical subjects

H Heimpel

Publications and source records attributed to H Heimpel.

At least 181 records · Page 10Linked to original sources

[Endocarditis caused by Haemophilus parainfluenzae and Neisseria gonorrhoeae].

Infective endocarditis due to gramnegative bacteria is rare. Overall, its relative frequency seems to be much lower than 10 percent. According to the extensive literature reviewed most often the causative microorganisms belong to the families of enterobacteriaceae and pseudomonads. Extremely rare, however, are cases where certain fastidious gramnegative bacteria such as hemophili, neisseria and others are the causative organisms. We report two cases of infective endocarditis due to Haemophilus parainfluenzae and to Neisseria gonorrhoeae. Despite their fastidious growth, both organisms could rapidly be isolated from venous blood cultures. Both were sensitive to ampicillin or penicillin respectively, and adequate antimicrobial therapy could early be initiated. As compared to reports in the literature both cases showed typical valve involvement and took a relatively typical course under medical treatment. The Haemophilus parainfluenzae endocarditis presented as a subacute illness following a tooth extraction and showed large vegetations on a prolapsed mitral valve. In contrast to the findings of others signs of slight renal involvement but no signs of major arterial embolization were noted. Medical treatment with ampicillin plus an aminoglycoside was effective as in most other reported cases. Vegetations were echocardiographically no longer seen after five weeks. The gonococcal endocarditis early led to destructive lesions of the aortic valve, significant regurgitation, vascular congestion and complicating pneumonia. Medical treatment alone was not effective despite the high susceptibility to antibiotics ot the strain isolated. As reported für the majority of cases reviewed in the literature early valve replacement became necessary for a favourable outcome.

Adult↗

Strategy for the treatment of hairy cell leukemia.

Both splenectomy and alpha-interferon are efficient treatments for hairy cell leukemia. Since interferon therapy seems to induce remissions of the disease, avoids the risks of surgery, and sustains the spleen, it should be discussed if this therapy may replace splenectomy as primary treatment for this disease. In order to make this decision the biologic relevance of complete remissions in hairy cell leukemia, the reliability of methods to confirm remission, the benefits and risks of both splenectomy and interferon therapy, and some aspects of the pathogenesis of the disease have to be considered. Based on our experimental and clinical results and data from other groups, we conclude that splenectomy should still be recommended as primary therapy in hairy cell leukemia provided that treatment is indicated and the patient is eligible for surgery.

Combined Modality Therapy↗

Treatment of aplastic anemia with cyclosporin A, methylprednisolone, and antithymocyte globulin.

Twenty-three patients with aplastic anemia (18/23 with severe aplastic anemia) were treated with an immunosuppressive regimen consisting of cyclosporin A (CsA) and methylprednisolone (MP) (n = 7) or CsA, MP, and antithymocyte globulin (ATG; n = 16). Nineteen patients are alive with a follow-up of 4 to 25 months; three patients died of infections and one of a gastrointestinal hemorrhage. Within 3 months, improvement of hematopoiesis was seen in 14 patients (61%). First signs of a response after 23 to 88 days were followed by complete remission in eight patients, partial remission in three patients, and minimal improvement in three patients. Two of the patients with only minimal improvement were treated with a second course of immunosuppression and reached a complete remission and partial remission. Interestingly, remission proved to be dependent on the continued administration of CsA in four of five patients with partial or complete remission who could be evaluated up to now. Thus, CsA must have been effective in the induction and/or maintenance of remission in three patients. This observation is a very strong argument for the role of T cells in the pathogenesis of at least some cases of aplastic anemia and warrants further evaluation of the role of CsA in the treatment of aplastic anemia.

Adolescent↗

HTLV III antibodies and immunological alterations in hemophilia patients.

The clinical, immunological, and serological status of 28 patients with hemophilia A and of 13 patients with hemophilia B was investigated. Thirty-four patients were treated regularly by clotting factor concentrates and 7 patients had been substituted only 1 to 4 times. Almost all patients with severe hemophilia suffered from hepatopathy. No patient had clinical evidence of the acquired immunodeficiency syndrome (AIDS). Asymptomatic hemophiliacs showed a decreased number of T-helper (OKT 4) cells and an increased number of T-suppressor (OKT 8) cells, which resulted in an inversed OKT 4/OKT 8 cell ratio. Natural killer cell activity of all patients was decreased compared to controls. After culture there was no significant difference of NK cell activity between hemophiliacs and controls. This phenomena was interpreted as a possible maturation defect of NK-cells in vivo. No relationship between immunological alterations and hepatopathy, hepatitis markers, CMV antibodies, amount and source of required factor concentrates, and the kind of hemophilia was observed. IgG immunoglobulins were higher and the OKT 4/OKT 8 ratio lower in the eight patients with lymphadenopathy than in patients without lymphadenopathy. The prevalence of antibodies to human T-lymphotropic virus (HTLVIII) was measured in 35 hemophiliacs and in 25 polytransfused patients, most of whom were suffering from acute leukemia. In 8 of 35 hemophiliacs antibodies to HTLVIII virus were detected by an enzyme linked immunosorbent assay (ELISA) and confirmatory tests. All seropositive patients were treated by blood products from the United States. Eight hemophiliacs treated by factor concentrates from German donors only were seronegative. In comparison 2 of 25 examined non-hemophilia patients receiving multiple blood products from local donors were seropositive for HTLVIII. The results show that hemophilia patients treated by imported clotting factor concentrates have a high risk of HTLVIII positivity. Hemophiliacs substituted by blood products obtained by local donor pools have only a small risk of infection. Because non-hemophiliac polytransfused patients had HTLVIII antibodies, there must be asymptomatic virus carriers in the local donor pool. The HTLVIII antibody screening of all donors and the heat treating of factor concentrates will give better therapeutic safety.

Acquired Immunodeficiency Syndrome↗

Deficient IFN alpha production in hairy cell leukemia.

Since the application of low doses of IFN-alpha is necessary to maintain remissions in Hairy Cell Leukemia (HCL) it is of interest whether peripheral blood mononuclear cells (MNC) of HCL patients can be induced in vitro to produce IFN-alpha. 9 patients suffering from advanced HCL were included in the study. The diagnoses were confirmed by characteristic findings in peripheral blood and bone marrow biopsies. For IFN treatment we initially used natural IFN-alpha (Bioferon) and switched later to recombinant IFN-alpha2 (Boehringer). MNC of 5 patients before IFN therapy and of 6 patients during IFN therapy (2-47 weeks) were induced by phytohemagglutinin (PHA), Corynebacterium parvum (C.p.), and sendai virus (SV). PHA is known to induce IFN-gamma. Both, C.p. and SV induced IFN-alpha but no IFN-gamma in MNC of healthy controls and of IFN treated breast cancer patients. In HCL patients normal antiviral activities could be induced by PHA. Zero or only low antiviral activities could be induced in MNC from 9 patients tested on 22 occasions. It is concluded that MNC from patients with advanced HCL can be induced to produce IFN-gamma but no IFN-alpha. Since IFN-alpha but not IFN-gamma is produced by monocytes it is likely that reduced numbers of monocytes which were found in our HCL patients before and during IFN treatment account for the described deficiency of IFN-alpha production.

Breast Neoplasms↗

Treatment results of nine patients with Burkitt's lymphoma.

From 6/79 until 2/86, 9 patients (median age 39) with Burkitt's lymphoma were treated. Stage D disease was seen in 7 cases, stage C in two and stage A in one. The main symptom was abdominal pain or a rapidly progressing abdominal tumor. Three patients had bone marrow involvement and two had a Burkitt's leukemia. Three had typical chromosomal aberrations. Therapy consisted of a variety of chemotherapy regimens plus additional radiotherapy and/or bulk surgery. Two patients achieved complete remissions (of 6 and 20+ months duration), and 4 partial remissions were obtained. The remaining patients had either progressive, drug resistant disease or died early. One patient is currently alive and in complete remission at 20+ months. A second patient is alive at 20+ months in partial remission with traces of IgM-paraprotein still detectable. The main causes of death were tumor-lysis syndrome (4 patients) and therapy related sepsis with progressive tumor (3 patients). This poor outcome is probably due to a high proportion of high-risk patients and suboptimal therapy for this rapidly proliferating tumor.

Adolescent↗

Biallelic heavy chain immunoglobulin gene rearrangement in acute nonlymphocytic leukemia.

Acute nonlymphocytic leukemia (ANLL) was diagnosed in 18 patients based on morphological, cytochemical and immunological criteria. Leukemic cells of these cases were subjected to Southern blot analysis and subsequent hybridization to heavy chain immunoglobulin and T-cell-receptor gene probes. A rearrangement within the immunoglobulin joining region was detected in 2 cases, while the T-cell-receptor beta-chain gene was in germline configuration in all samples investigated. These data confirm recent reports indicating that immunoglobulin heavy chain gene rearrangements are not restricted to B-lineage neoplasms.

Adult↗

Cyclosporine as an alternative to cyclophosphamide in the treatment of chronic graft-versus-host disease.

Four patients with progressive extensive chronic graft-versus-host disease or dose-limiting toxicity on conventional therapy (cyclophosphamide + prednisolone) were treated with a regimen of cyclosporine + prednisolone as induction therapy and cyclosporine as maintenance therapy. All 4 showed clinical improvement and 3 of 4 are alive at 9 months. The incidence of infections was not affected by this regimen, but steroid requirements were reduced.

Acute Disease↗

Ex vivo T-cell depletion with the monoclonal antibody Campath-1 plus human complement effectively prevents acute graft-versus-host disease in allogeneic bone marrow transplantation.

We have developed a rapid and simple procedure for the elimination of mature T-cells from the donor marrow using a single incubation with the monoclonal antibody Campath-1 and donor complement. This resulted in a reduction of T-cell contamination to a mean of 1%. This regimen reduced the incidence of acute graft-versus-host disease significantly in 21 consecutive bone marrow grafts in 18 patients with leukaemia and non-Hodgkin's lymphoma. Purging was responsible for an increased incidence of graft rejection in HLA-identical transplants (13%).

Adolescent↗

Immunoglobulin substitution therapy in a patient with primary hypogammaglobulinaemia and anti-IgA antibodies.

Permanent immunoglobulin substitution therapy was performed in a 44-year-old patient with common variable immunodeficiency, recurrent respiratory tract infections, total absence of serum IgA and a high titre of class-specific anti-IgA antibodies. An IgA-depleted i.v. immunoglobulin (IG) preparation was used. Infusions were well tolerated by the patient although minor anaphylactoid symptoms regularly occurred. Anti-IgA antibody titres rose during the first 4 months of treatment and gradually fell during the following 8 months. Regular IG substitution therapy led to a substantial improvement in the patient's health and quality of life.

Adult↗

Acute hematotoxicity of oral benzo(a)pyrene: the role of the Ah locus.

Our results show a marked acute hematotoxicity of oral benzo(a)pyrene (BaP) in D2 mice as well as the extreme resistance of BDF1 individuals to bone marrow toxicity induced by oral BaP. Continued oral BaP produced severe bone marrow depression in D2 mice affecting all myelopoietic lineages, but produced only moderate bone marrow depression in BDF1 mice affecting erythropoiesis only. Pluripotent hematopoietic stem cells were almost completely destroyed in D2 individuals, but only reduced to approximately 40% in BDF1 individuals after 7 days of BaP. D2 mice were killed by 13 days of continued oral BaP, but BDF1 mice were still alive and in good condition even after 19 days of continued oral BaP. Analysis of the bone marrow and peripheral blood changes showed that severe toxic chemical bone marrow depression in D2 mice by continued oral BaP cannot serve as an experimental model system of acute aplastic anemia.

Animals↗

TAD-induction therapy for 175 adults with acute myeloid leukemia, followed by consolidation and maintenance therapy. The joint study of Ulm and Tübingen.

175 patients with acute myeloid leukemia were treated between February 1980 and March 1985 with a TAD-induction therapy, three intensified consolidation cycles (COAP, COAP, AD), and a two-year mild maintenance therapy. The median age of the patients was 44 years, range 15-68 years. 62.3% of all patients attained complete remission and 13.7% partial remission. The median duration of remission was 10 months and the median survival time of patients in complete remission was 20 months. Patients older than 50 years had a higher early death rate (17.6) than younger patients (8.9%), but no difference was found in remission rates or in the median duration of remission and of survival. These results are in line with those of comparable studies.

Adolescent↗

Hemopoietic reconstitution after bone marrow transplantation.

Forty-one patients underwent bone marrow transplantation (BMT) for treatment of severe aplastic anemia or hematologic malignancies. Hemopoietic reconstitution after BMT was monitored by peripheral blood counts, counts of bone marrow cellularity, and clonal assays for hemopoietic progenitors (CFUc, CFUe, and BFUe), along with bone marrow morphology. The number of transplanted nucleated cells and the number of transplanted progenitors (CFUc, CFUe, and BFUe) correlated significantly with the time of reticulocyte recovery. The number of transplanted CFUc correlated significantly with the time of granulocyte recovery. Platelet recovery occurred late and showed large variations. No correlation between the transplanted cells and the recovery of nucleated cells or hemopoietic progenitors (CFUc, CFUe, and BFUe) in the bone marrow was found. Bone marrow cellularity and hemopoietic progenitors showed a rapid, but incomplete, recovery during the first 56 days after BMT. Hematologic studies on seven long-term survivors with an uncomplicated posttransplantation course revealed subnormal bone marrow cellularity and hemopoietic progenitor incidence up to three years after BMT, despite normal peripheral blood counts. The low progenitor incidence could be explained by a proliferative defect of the stem cells, compensated for by an amplification in the more differentiated compartment of hemopoiesis.

Anemia, Aplastic↗

Hematopoietic colony formation after allogeneic bone marrow transplantation: enhancement by cyclosporin A and anti-gamma-(immune) interferon antiserum in vitro.

Bone marrow hematopoietic progenitors (CFU-GM, CFU-E, and BFU-E) were found to be markedly decreased in 21 bone marrow transplant recipients studied from one to 51 months after transplantation. In these patients, bone marrow colony formation could be significantly enhanced by in vitro incubation of the bone marrow target with cyclosporin A (CyA; 0.5 microgram/ml) or with a monoclonal anti-gamma-(immune) interferon (IFN-gamma) antibody. Both effects were highly correlated. The data indicate that (a) endogenous elaboration of IFN-gamma may contribute to decreased colony formation in allogeneic bone marrow transplant recipients, and (b) CyA may induce a gradual release of the progenitor cell pool from IFN-gamma-mediated suppression.

Antibodies, Monoclonal↗