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Biomedical subjects

C Nissen

Publications and source records attributed to C Nissen.

At least 19 recordsLinked to original sources
PubMed1992

Morphology in patients with severe aplastic anemia treated with antilymphocyte globulin.

One hundred and seventeen patients with severe aplastic anemia (SAA) were treated at our institution between 1976 and 1990 with antilymphocyte globulin (ALG) therapy. Seventy-nine (68%) are alive and probability of survival at 14 years, according to Kaplan and Meier, is 62% +/- 12%. Twenty-six patients developed a late clonal complication: 11 had a myelodysplastic syndrome (MDS) and 17 had paroxysmal nocturnal hemoglobinuria (PNH); two patients had both. The cumulative risk at 10 years is 42%. The development of MDS/PNH after SAA directly affects survival. The probability of being alive at 14 years is 81% +/- 10% for patients with stable disease and 36% +/- 13% for those with clonal evolution (P = .001). To look for predictive signs, we reevaluated peripheral blood and bone marrow cytomorphology at presentation, during regeneration, and in remission. We examined the peripheral blood values for hemoglobin, reticulocytes, granulocytes, thrombocytes, mean corpuscular volume (MCV), and fetal hemoglobin, as well as bone marrow for cellularity, erythropoiesis, myelopoiesis, and megakaryopoiesis. ALG therapy induces slow and incomplete recovery. Although in "remission," ALG patients have lower hemoglobin values, higher reticulocyte counts, lower granulocyte and platelet values, and a higher MCV and fetal hemoglobin than normal controls. They retain a reduced number of megakaryocytes and a persistence of atypical monocytes in bone marrow morphology as stigmata of their disease. Patients with late clonal complications show distinct morphologic abnormalities: patients with PNH have higher MCVs, higher granulocyte and reticulocyte counts, and more dyserythropoiesis at diagnosis and a lower hemoglobin with an increased proportion of erythroblasts in the bone marrow in "remission." Patients who later developed MDS are not different from the total patient population at diagnosis. After therapy, these patients are characterized by the presence of ring sideroblasts and atypical monocytes during regeneration and by a persistent increase in MCV, a higher fetal hemoglobin, lower granulocyte values, and megakaryocytic dysplasia during "remission." Thus, routine morphologic follow-up examination of blood and bone marrow can discover patients at risk for late hematologic complications after ALG therapy.

Adult↗
PubMed1992

Stem cell factor stimulates the in vitro growth of bone marrow cells from aplastic anemia patients.

Aplastic anemia (AA) is a rare human bone marrow disorder of unknown etiology manifested by a strongly impaired growth of hematopoietic precursors. In this study, we examined the ability of recombinant human stem cell factor (SCF) to stimulate proliferation in vitro of bone marrow cells from 15 AA patients. All patients had been previously treated with antilymphocyte globulin (ALG). SCF, in combination with erythropoietin (Epo), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF), increased the number of hematopoietic colonies formed in a semisolid medium by AA marrows. Maximal colony numbers reached 30% of the numbers observed with normal bone marrow cells. Proliferation of AA cells cultured in a liquid medium containing SCF together with Epo, IL-3, GM-CSF, and G-CSF approached 70% of the control level, as measured by 3H-thymidine incorporation. The effect of the combination of SCF with the other growth factors was more than 10 times stronger than that of the growth factors alone. The most marked effect of SCF was on the generation of erythroid colonies by precursor cells. The results demonstrate synergism between CSF and other hematopoietic growth factors, resulting in the most efficient stimulation of the in vitro growth of AA bone marrow cells described to date. Use of SCF, either alone or in combination with other factors, may be of potential value in treatment of AA.

Adolescent↗
PubMed1992

Recombinant human granulocyte-macrophage colony-stimulating factor accelerates neutrophil and monocyte recovery after allogeneic T-cell-depleted bone marrow transplantation.

In a prospective randomized study, five European transplant centers compared recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; mammalian glycosylated) with placebo. rhGM-CSF was administered in a dose of 8 micrograms glycoprotein (5.5 micrograms protein)/kg/d, as a continuous intravenous (IV) infusion for 14 days, starting 3 hours after bone marrow infusion. Fifty-seven patients entered and completed the study. Median age of the recipients was 34 years (range, 17 to 51 y). All donors were HLA-identical, MLC-nonreactive siblings. Marrow grafts were depleted of T lymphocytes either by counterflow centrifugation (n = 42) or by immunological methods (n = 15). Twenty-nine patients received rhGM-CSF and 28 patients placebo. The leukocyte count and the absolute neutrophil count were significantly higher in the rhGM-CSF-treated group from day +9 to day +14 after bone marrow transplantation (BMT). This was also true for the monocyte count from day +12 to day +21. Early neutrophil (greater than 0.1 and greater than 0.3 x 10(9)/L) and early leukocyte (greater than 0.3 and greater than 0.5 x 10(9)/L) recovery was significantly faster for the patients given GM-CSF. The incidences of graft-versus-host disease (GVHD) and transplant-related mortality were not different in both groups. However, the number of bronchopneumonias was significantly lower in the rhGM-CSF-treated group (P = .03). Long-term follow-up showed a trend to better overall disease-free survival at 2 years and a trend to a lower relapse risk in patients treated with rhGM-CSF. This study shows that rhGM-CSF significantly increases neutrophil and monocyte counts during periods of 6 to 10 days in the second and third week after BMT. This shortened period until myeloid cell recovery after transplantation resulted in a decreased number of pneumonias, without an increase in incidence of GVHD or relapse.

Adolescent↗
PubMed1992

Human serum stimulates the production of G-CSF, IL-1, IL-6 and IL-8 by human peripheral blood leucocytes.

Human serum induces human peripheral blood leucocytes (PBL) to release an activity stimulating neutrophil colony formation (G-CSA) from human bone marrow cells. By titrating individual growth factors and using specific neutralizing antibodies we showed that: human serum contains very low levels of G-CSF which are by themselves insufficient to stimulate myeloid colony formation in primary human bone marrow cultures and cannot account for the serum releaser activity; that although no detectable levels of IL-1, IL-2, IL-3, IL-4, IL-6 or IL-8 are found in the serum, anti IL-1 antibodies partially block the release of G-CSA when added early during PBL incubation; that PBL incubated in the absence of serum for 2 d produce small amounts of IL-1, IL-6, IL-8 and G-CSF and this is increased 6-16 fold in the presence of human serum; and that the neutrophil colony-stimulating activity released by PBL incubated with human serum is G-CSF.

Biological Assay↗
PubMed1992

Suspected distinct activation pathways of human lymphocytes induced by antilymphocyte globulin and anti-CD3 monoclonal antibody result in different secretion of hematopoietic colony-stimulating activities.

We evaluated the activation sequence of peripheral blood lymphocytes from healthy donors using different mitogens, including antilymphocyte globulin (ALG), anti-CD3 monoclonal antibody (OKT3), and phytohemagglutinin (PHA). Blood mononuclear cells stimulated by ALG, OKT3 and PHA incorporated 3H-thymidine in the same way. When enriched T cells were tested in the presence of interleukin-1 alpha (0 to 100 U/ml, incorporation of 3H-thymidine was greater in those cells stimulated by ALG than by PHA. OKT3 did not activate enriched T cells. Thymidine incorporation was reduced to less than 50% of maximum concentrations by the addition of 10(-7) mol/1,25-dihydroxyvitamin D3 (vit D3) in PHA- or OKT3-activated cells. However, the inhibitory effect of vit D3 was not apparent in ALG-activated cells. Production of granulocyte-macrophage colony-stimulating factor and interleukin-3 by lymphocytes upon activation was consistently higher when cells were treated with ALG or PHA than with OKT3. Taken together, the data indicate that there appear to be distinct functional mechanisms between ALG- and OKT3-induced lymphocyte activation that lead to characteristic immunohematologic events.

Antibodies, Monoclonal↗
PubMed1991

[Health status and late complications following allogeneic bone marrow transplantation. A review].

Better results following bone marrow transplantation (BMT) have increased the number of patients in longterm follow-up. Health status and late effects are therefore of increasing interest. We discuss here the incidence and follow-up of late complications after allogenic BMT. Any conditioning regimen including TBI in postpubertal women introduces a postmenopausal status. In contrast, normal function is found after BMT without irradiation. In men, there is usually permanent azoospermia after TBI but not following chemotherapy alone. Thyroid dysfunction after BMT with TBI has been reported in about 40% of patients. In most of them compensated hypothyroidism with elevated TSH is found. BMT with TBI induces growth retardation in children. Decreased growth hormone levels are observed and substitution can induce normal height development. Interstitial pneumonitis (IP) is a major cause of death. It occurs on average three months after BMT but late onset IP's are increasingly reported. Cataracts are common after BMT. The risk of cataracts in patients given single dose TBI attains 80-100% after four years. Under treatment with cyclophosphamide alone, the risk of lens opacification is less than 20%. So far, patients treated with fractionated TBI have not developed more cataracts than those treated with chemotherapy alone. Impaired renal function is common early post-transplant. Risk factors include cyclosporine (CSA) nephrotoxic antibiotics and antifungal drugs. So far, few secondary malignancies have been reported in humans after BMT. However, actual observation time is still too short for final evaluation. Prevention or treatment is instituted for common complications. It is expected that other types of tissue damage will be recognized.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Serum concentrations of immunoglobulins and of antibody isotypes in bone marrow transplant recipients treated with high doses of polyspecific immunoglobulin or with cytomegalovirus hyperimmune globulin.

The kinetics of immunoglobulins (Ig) and antibodies were followed in 10 bone marrow transplant recipients who received either high doses (0.5 g/kg body weight) of polyspecific intravenous Ig (HD-IVIG) weekly or cytomegalovirus hyper-Ig (CMV-IVIG, 0.1 g/kg body weight) every 3 weeks. In the HD-IVIG group, the mean total IgG concentration more than tripled and similar significant increases were seen for IgG1 and IgG2. IgG antibodies to CMV showed a marked increase in the HD-IVIG and a less pronounced rise in the CMV-IVIG group. IgM antibodies to CMV were present initially or became detectable in five patients, unrelated to the IVIG preparation. HD-IVIG induced a significant increase of IgG antibodies to streptococcal group A carbohydrate (A-CHO) and to smooth strain lipopolysaccharides (LPS) but not of antibodies against lipid-A. When the Ig treatment was discontinued, levels of total IgG and of IgG antibody to CMV decreased with an apparent half-life of 30 days. Both IVIG preparations were well tolerated and had no negative feedback on total Ig and on specific antibody production or other antimicrobial defence mechanisms. In patient nos. 4 and 10 who developed severe graft-versus-host-disease, transient serum Ig peaks including several Ig isotypes appeared after day 14. In patient no. 10 this peak contained an IgG antibody to H. influenzae type b (Hib), and IgM antibodies to CMV, Hib, A-CHO and LPS. This study clearly shows that serum concentrations of Ig isotypes, subtypes and specific antibodies, depend on at least four factors: total amount and composition of Ig infused, consumption, catabolism and endogenous production.

Adult↗
PubMed1991

The pathophysiology of aplastic anemia.

No single cause can explain aplastic anemia. Two major factors are involved: An intrinsic derangement of hemopoietic proliferation capacity that is essentially compatible with life, but has to be considered a premalignant condition. This primarily diseased tissue can be destroyed by immune mechanisms in an attempt to achieve self-cure. Therefore, immunosuppressive therapy can mitigate this immune reaction but leaves the patient with a poorly proliferating bone marrow that is prone to late complications. The clinical presentation and course depend on the balance of these two major factors: If the immune reaction is strong, acute severe aplasia occurs, whereas in patients with a weak immune reaction the disease will present itself rather as chronic pancytopenia with myelodysplastic traits. Co-involvement of environmental cells in the disease process is an additional factor. Poor production of hemopoietic growth factors may aggravate aplasia and poor immune competence may allow abnormal clones to proliferate. All these pathophysiological factors are genetically determined.

Anemia, Aplastic↗
PubMed1990

Cytotoxic and stimulatory effects of antilymphocyte globulin (ALG) on hematopoiesis.

Four different preparations of antilymphocyte/antithymocyte globulin were tested in vitro for their toxicity to lymphocytes and to hematopoietic precursor cells, depending on concentration and time. Complete lymphocytotoxicity was observed at concentrations from 6.3 to 25 micrograms/ml, and suppression of colony formation by hematopoietic precursors was seen at concentrations from 12.5 to 250 micrograms/ml. Prolonged incubation time did not increase lymphocytotoxicity but augmented precursor cell damage. Lymphocytotoxicity was comparable among the four preparations tested whereas precursor cell toxicity varied widely. Antilymphocyte globulin is mitogenic and stimulates the release of hematopoietic growth factor activity by peripheral blood cells. Absorption of ALG with human T-cells eliminated precursor cell toxicity and mitogenicity but not the capacity to release hematopoietic growth factors. These results show that dose/time schedules for ALG administration may be relevant and ALG acts by virtue of inhibitory and stimulatory antibody effects.

Antilymphocyte Serum↗
PubMed1990

Evaluation of the Sysmex R-1000. An automated reticulocyte analyzer.

The new fully automated reticulocyte analyzer, Sysmex R-1000 (TOA Medical Electronics, Kobe, Japan), was evaluated for its routine use in the Hematological Laboratory at the University Hospital Basel, Switzerland. The operating characteristics, such as within-run precision, linearity, and carryover, fulfilled the manufacturer's specifications and are excellent. Correlation with the standard method, manual reticulocyte counting, is linear for normal and high values. For low reticulocyte counts the regression points show a deviation from their linearity. An absolute zero value is not obtained by the R-1000. The R-1000 measures total RNA content of each cell and expresses the value as low fluorescence ratio (LFR), medium fluorescence ratio (MFR), and high fluorescence ratio (HFR). The analysis of this ratio resolves the problem of zero reticulocytes: A fraction of less than 0.002 (0.2%) with an LFR of 100% represents aplasia; a shift of the intensity of fluorescence to HFR heralds regeneration. Results of samples stored at room temperature remain stable and within the range of the within-run precision for up to 12 hours, when stored at 5 degrees C for more than 48 hours. The authors conclude that the R-1000 is easy to operate, fulfills the criteria for accuracy and precision, and is highly suitable for daily routine use in a large central hematologic laboratory.

Autoanalysis↗
PubMed1990

Chronic cyclosporine-associated nephrotoxicity in bone marrow transplant patients.

This study describes the prevalence and degree of chronic cyclosporine-associated nephropathy and its risk factors. For this purpose we reviewed all available renal histology specimens in 169 bone marrow transplant recipients treated during an eight year period with cyclosporine for prevention of graft-versus-host-disease, and determined their pattern and degree of histomorphological changes. A total of 51 specimens obtained from 49 patients by biopsy (n = 12) or autopsy (n = 39) was evaluated. The pattern of histomorphological changes was compared with diagnosis, age, sex, and potential risk factors--such as cyclosporine dose, levels, duration of therapy, changes in serum creatinine and onset of hypertension. Morphological lesions of chronic cyclosporine-associated nephropathy were found in 67% of the specimens. They were more frequent and more severe with increasing duration of cyclosporine therapy, in patients with a higher increase in serum creatinine during the first 3 months and in patients given total-body irradiation for conditioning. These latter findings suggest that additional damage sensitizes the kidney to irreversible toxic effects of cyclosporine.

Adolescent↗