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Biomedical subjects

W Heit

Publications and source records attributed to W Heit.

At least 55 records · Page 3Linked to original sources
PubMed1986

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↗
PubMed1986

Human leukemic cells: receptor binding and biological effects of insulin and insulin-like growth factors.

Receptor binding and biological effects of insulin and insulin-like growth factors I and II (IGF I/II) were assessed in three human malignant cell lines: a Burkitt-type ALL-cell line, a ANLL-cell line and a Hodgkin's disease-cell line. Insulin receptor binding could be demonstrated in Burkitt-type ALL cells and ANLL cells, whereas no insulin receptor binding was detectable in Hodgkin cells. IGF I and IGF II binding could be demonstrated in all leukemic cells. Insulin stimulated glycogen synthesis in the insulin receptor bearing cell lines. DNA synthesis was stimulated by insulin, IGF I and II. IGF I was more active in stimulating DNA synthesis than IGF II.

Cell Line↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

Host-reactive cytotoxic T lymphocyte precursors in long-lived fully allogeneic mouse bone marrow chimeras.

Fully H-2-incompatible chimeric mice were constructed by grafting lethally (950 rad) irradiated germ-free (GF) CBA (H2k) mice with anti-Thy 1 antibody plus complement-treated allogeneic C57Bl/6 (B6) (H2b) bone marrow cells. These chimeric mice were kept for more than 11 months, either under GF conditions or under barrier-sustained specific-pathogen-free (SPF) conditions. Controls included nonirradiated, nontransplanted, sex- and age-matched CBA and B6 mice raised under SPF conditions, and syngeneic chimeric mice of the CBA----CBA type kept under GF and SPF conditions. All chimeric mice were completely repopulated with donor-type lymphoid cells and showed no clinical or histological evidence of graft-versus-host disease. From the fully allogeneic chimeric mice, we enumerated the numbers of splenic cytotoxic T lymphocyte precursors (CTL-p) that could be clonally expanded under limiting dilution conditions in response to third-party alloantigens, or nonmodified and trinitrophenyl (TNP)-modified stimulator cells bearing host or donor H-2 antigens. The existence of high numbers of alloreactive and host- or donor-type H-2-restricted TNP-specific CTL-p in the spleens of fully allogeneic chimeras indicated almost normal immunocompetence. The surprising finding, however, was that large numbers of host (CBA)-reactive splenic CTL-p were inducible under limiting dilution conditions in healthy long-lived allogeneic chimeras, although these chimeric mice were devoid of any histological or clinical signs of graft-versus-host disease.

Animals↗
PubMed1986

Human fetal and adult chondrocytes. Effect of insulinlike growth factors I and II, insulin, and growth hormone on clonal growth.

Clonal proliferation of freshly isolated human fetal chondrocytes and adult chondrocytes in response to human insulinlike growth factors I and II (IGF I, IGF II), human biosynthetic insulin, and human growth hormone (GH) was assessed. IGF I (25 ng/ml) stimulated clonal growth of fetal chondrocytes (54 +/- 12 colonies/1,000 inserted cells, mean +/- 1 SD), but IGF II (25 ng/ml) was significantly more effective (106 +/- 12 colonies/1,000 inserted cells, P less than 0.05, unstimulated control: 14 +/- 4 colonies/1,000 inserted cells). In contrast, IGF I (25 ng/ml) was more effective in adult chondrocytes (42 +/- 6 colonies/1,000 inserted cells) than IGF II (25 ng/ml) (21 +/- 6 colonies/1,000 inserted cells; P less than 0.05, unstimulated control: 6 +/- 3 colonies/1,000 inserted cells). GH and human biosynthetic insulin did not affect clonal growth of fetal or adult chondrocytes. The clonal growth pattern of IGF-stimulated fetal and adult chondrocytes was not significantly changed when chondrocytes were first grown in monolayer culture, harvested, and then inserted in the clonal culture system. However, the adult chondrocytes showed a time-dependent decrease of stimulation of clonal growth by IGF I and II. This was not true for fetal chondrocytes. The results are compatible with the concept that IGF II is a more potent stimulant of clonal growth of chondrocytes during fetal life, whereas IGF I is more effective in stimulating clonal growth of chondrocytes during postnatal life.

Adult↗
PubMed1986

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↗
PubMed1986

Pyrazolone drugs and agranulocytosis.

Ever since mass consumption of chemically pure drugs started at the beginning of this century, cases of agranulocytosis have been reported in the literature. These were very soon seen as being causally related to drug use. The present paper discusses the clinical symptoms of the disease, the possibilities of its treatment, and the obvious connections between the use of pyrazolone drugs and the occurrence of agranulocytosis.

Agranulocytosis↗
PubMed1985

Drug-induced agranulocytosis: evidence for the commitment of bone marrow haematopoiesis.

Clinical and haematological features of 61 patients with drug-induced agranulocytosis (63 episodes) are presented. Multiple drug consumption was a common observation and complicated the attempt to incriminate a particular drug as being aetiologically involved. Bone marrow analysis shortly after the diagnosis revealed evidence for an impairment of proliferative granulopoiesis in the majority of cases. This observation was confirmed by in vitro culturing of granuloid precursor cells (CFU-c). Moreover, the data clearly demonstrated that drug-induced agranulocytosis may not be restricted to the granulocytic series. Thrombocytosis and reticulocytosis during the recovery phase are taken as an indication for the commitment of all haemopoietic cell lineages in agranulocytosis. These observations were in accordance with cytomorphological studies and in vitro culture data of erythroid precursor cells (CFU-e, BFU-e) of bone marrow aspirates taken in the initial phase of agranulocytosis. More than 25% of the patients showed a marked erythroid depression in the marrow.

Adolescent↗
PubMed1985

Modified immunocytochemical slide technique for demonstrating surface antigens on viable cells.

Further developments of an immunoenzymatic slide technique to demonstrate cell surface antigens with monoclonal antibodies are described. In this method cells are attached to polylysine coated glass slides in order to facilitate the handling of low cell numbers and to save antibodies and time for washing the cells. The technique has been modified for the labelling of viable cells. Endogenous peroxidase is used as an additional cell marker which does not interfere with the demonstration of antigens on the cell surface by immunoperoxidase methods. Damaged cells can be identified reliably, thereby minimising interpretation errors due to non-specific antibody uptake. A double labelling technique employing peroxidase and alkaline phosphatase coupled reagents is presented. Results of this slide technique are clear cut, so that evaluation can be performed by trained technicians.

Alkaline Phosphatase↗
PubMed1985

[Risk factors for the occurrence of pneumonia caused by cytomegaloviruses in patients with bone marrow transplants during prevention with cytomegalovirus hyperimmune globulin].

After bone marrow transplantation (BMT) transient combined immunodeficiency occurs which promotes the occurrence of severe cytomegalovirus (CMV) infections, the most frequent lethal complication at present. 28 patients received a CMV-IgG-hyperimmunoglobulin (CMV-IG) intravenously as CMV-prophylaxis. The efficacy of this treatment and the risk factors for the occurrence of interstitial pneumonia (IP) caused by CMV were analyzed. Risk factors promoting a CMV-IP were: immunosuppression after BMT, CMV-seropositivity of recipient and donor, granulocyte transfusions and HLA-mismatched BMT. In this study graft versus host disease did not influence the occurrence of CMV-IP.

Adult↗
PubMed1985

Clonal proliferation and cell density of chondrocytes isolated from human fetal epiphyseal, human adult articular and nasal septal cartilage. Influence of hormones and growth factors.

The present study characterizes the cell density and cellular growth characteristics of functionally and morphogenetically different human cartilages. In fetal epiphyseal, in postnatal nasal septal and in articular cartilage the influence of aging on cell density and in vitro growth characteristics were investigated. Cell density was highest in fetal epiphyseal cartilage and lowest in articular cartilage. In vitro growth of isolated chondrocytes as measured by clonal growth in a semisolid assay was almost identically high in fetal epiphyseal and septal cartilage and significantly lower in articular cartilage. Cell density increased with age in the nasal septal cartilage whereas no age dependency was found in the other cartilages. The stimulatory effects of human biosynthetic insulin, human growth hormone and partially purified IGF I on clonal growth of chrondrocytes were assessed. Only IGF I stimulated clonal growth of chondrocytes and its stimulatory effect was significantly higher in postnatal than in fetal chondrocytes.

Adolescent↗
PubMed1984

[Bone marrow transplantation in panmyelopathy, acute leukemia and chronic myelocytic leukemia: results of the Ulm Transplantation Group].

From 1972-1983 53 patients underwent bone marrow transplantation. The median age was 18 years (3-41). 27 patients suffered from severe aplastic anaemia, 22 patients had acute leukaemia and 4 patients had chronic granulocytic leukaemia in chronic phase. Out of 22 patients with acute leukaemia, 2 had florid leukaemia, 2 had an early relapse and 18 patients were in first or second remission of their disease. 2/53 patients received a syngeneic transplant, 51/53 patients an allogeneic transplant. 47/51 patients had a HLA-A, B, C-identical, MLC-negative sibling donor, 1/51 had a HLA-A, B-C-identical, MLC-positive sibling donor, 2/51 a HLA-phaenotypical identical parental donor and 1/51 a HLA-identical, MLC-negative unrelated donor. The comparison of the results obtained in patients with severe aplastic anaemia transplanted from 1972-1979 with those transplanted from 1980-1983 shows that the bone marrow transplantation has to be performed in an early stage of the disease before the patients become multiple transfused, sensitized and severely infected and that the conditioning regimen for polytransfused patients has to be more intensive than in untransfused patients. From the patient group transplanted 1972-1979, only 1/14 patients is a long-term survivor in contrast to 8/13 patients transplanted from 1980-1983. 11/22 patients with acute leukaemia are alive between more than 5 years and 14 days after bone marrow transplantation. Only 1/4 patients, who were transplanted not in remission, is alive.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1984

Agranulocytosis associated with semisynthetic penicillins and cephalosporins. Report of 7 cases.

Within one year we observed in the same intensive care unit seven severely polytraumatized patients with agranulocytosis (AG) associated with treatment by semisynthetic penicillins or cephalosporins combined with aminoglycosides. Antibiotics were given because of severe bacterial respiratory or generalised infections. Five patients died, four of them without haematological remission. Bone marrow aspirates showed hypoplasia of granulopoiesis due to a lack of mature cells. Leukocyte and granulocyte counts in the blood declined continuously over a period of 8 to 11 days. In average, minimal granulocyte counts occurred after 21 days of hospitalisation and 14 days of antibiotic drug exposure. Beside the incriminated antibiotics all patients were treated sporadically with other agents of which may cause AG. Granulocyte kinetics and serial bone marrow examinations of one patient suggest a phenothiazine type of AG, which is caused by a toxic damage of granulopoiesis. Declining absolute granulocyte counts in the blood together with persisting high temperatures during antibiotic treatment should give rise to the suspicion of a beginning AG.

Adult↗
PubMed1984

Patterns of growth in human septal cartilage: a review of new approaches.

Recent results of the growth activities of the septal cartilage in children, adolescents, and adults are reviewed. Cartilaginous biopsies were obtained during septoplasty . Matrix synthesis was measured by in vitro incorporation of labeled sulphate; DNA synthesis was measured by in vitro incorporation of labeled thymidine. The cell density of the septal cartilage was determined by cell counting, and chondrocytes were grown in culture in an assay to determine the number of chondrocytes capable of proliferation. With data from these 4 types of experiments 5 different areas could be distinguished in human septal cartilage: (1) anterior free end, (2) suprapremaxillary area, (3) central area, (4) posterior area, and (5) caudal prolongation. Metabolic activities, degree of cell replication, and proliferative capacity are highest in childhood in all areas; they decline with age, but remain surprisingly high in the central area and in the anterior free end, even in adults. These results help to explain some clinical observations and may help the rhinosurgeon in his decision to resect the septal cartilage, especially in children.

Adolescent↗
PubMed1984

Growth of the human septal cartilage: cell density and colony formation of septal chondrocytes.

Human chondrocytes from 24 patients (5 to 52 years) with septal deviation were isolated in different areas of the septal cartilage. Cell density was counted, and the chondrocytes were grown in an assay system for determining the number of chondrocytes capable of proliferating. High cell density and excellent proliferative capacity were found in the anterior free end of the septal cartilage in all age groups. The central area showed the highest growth index in childhood, and increasing cell density from childhood to puberty. Generally the growth index decreased with age in all septal areas. The results help to explain some clinical observations: increasing septal cartilage even in adults, growth of nasal tip in adults, regenerative potential of septal cartilage after injuries or surgery, importance of the central area for septal growth and surgery.

Adolescent↗