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Biomedical subjects

A Gratwohl

Publications and source records attributed to A Gratwohl.

At least 289 records · Page 16Linked to original sources
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

Hematologic values of New Zealand white rabbits determined by automated flow cytometry.

Hematologic values of peripheral blood from normal adult New Zealand White rabbits were determined by five different automated flow cytometers in use in a routine clinical hematology laboratory: Technicon H1, Coulter Counter CC540, Coulter Counter VCS, Sysmex NE8000 and Sysmex R1000. The software designed for human blood analysis was used in all instances without adaptation. The total numbers of white blood cells, red blood cells, reticulocytes and platelets were measured with high precision and accuracy. Except for hemoglobin content, concordance was excellent for all measured and calculated values among the different automated flow cytometers. Determining the white blood cell differential count was more complex. Eosinophils and lymphocytes were quantified reliably by all the automated flow cytometers used. However, the results were rejected by Technicon H1 and Sysmex NE8000 in 50% of the cases. Rabbit basophils were recognized with accuracy by Technicon H1 only. The proportion of polymorphonuclear versus mononuclear white cells was identical when measured with Technicon H1 and Coulter Counter VCS. These results show that the new generation of automated flow cytometers designed for human blood can be used with some limitations for animal studies. They allow the standardization of normal values and comparison of results among or between laboratories. They also introduce new parameters, the value of which is as yet undefined.

Animals↗
PubMed1991

Bone marrow transplantation activity in Europe 1990. European Group for Bone Marrow Transplantation (EBMT)

During 1990 143 teams in 20 European countries performed a total of 4234 bone marrow transplants. Donor source was in 1802 cases an HLA-identical family donor, in 118 cases a non-identical family donor, in 36 cases a twin donor, in 181 an unrelated volunteer donor and in 2097 cases autologous bone marrow. Indications for the transplant were leukaemias in 2365 patients, lymphoproliferative disorders in 1104 patients, solid tumours in 382 patients, aplastic anaemia and thalassaemia in 281 patients, inborn errors in 58 patients and miscellaneous disorders in 44 patients. This survey of the European Group for Bone Marrow Transplantation on transplant activity clearly indicates that within the last decade bone marrow transplantation has become an established therapy in Europe. The results of this first complete survey provide a basis for planning therapeutic trials and health policy strategies.

Anemia, Aplastic↗
PubMed1991

Allogeneic bone marrow transplantation in chronic lymphocytic leukemia: 17 cases. Report from the EBMTG.

Allogeneic bone marrow transplantation (BMT) was performed in 17 patients with chronic lymphocytic leukemia (CLL): 15 resistant and two untreated forms. There were 12 males and five females with a mean age of 40 years (32-49). The conditioning regimens and graft-versus-host disease (GVHD) prophylaxis varied. Successful engraftment was obtained in 15 evaluable cases. Lymphocytosis and clinical symptoms subsided in all but one case. All 15 evaluable patients developed acute GVHD. Among the 17 patients grafted, one early death was observed at the 15th day post-BMT, and one refractory patient died 2 months after BMT. Of the remaining 15 patients in complete remission (CR), four died from GVHD, hemorrhage and graft failure, and two relapsed at 7 and 54 months after BMT and died. Nine patients are alive in CR with a mean follow-up of 25.6 months (4-48). Chimerism was complete in eight patients and partial in the two T cell-depleted cases. In one case, an immunoglobulin gene rearrangement study showed no residual disease. These results suggest that allogenic BMT might be an alternative and possible curative therapy for refractory CLL in young patients when performed relatively early in the disease.

Adult↗
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

Bone marrow transplantation: indications and technique.

Bone marrow transplantation has emerged during the last two decades from a highly experimental procedure to an accepted therapeutic modality which is carried out at more than 175 institutions worldwide. This paper summarises the indications for this therapy and describes, in short, the techniques of the different consecutive steps involved in bone marrow transplantation.

Bone Marrow Transplantation↗
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↗
PubMed1990

Lethal cyclosporine associated toxicity in the rabbit: similar findings in two distant and independent transplant laboratories.

A collaborative study was initiated between Basel and Irvine Laboratories named above in an attempt to characterize a unique and lethal gastrointestinal toxicity in rabbits associated with cyclosporine administration. Data from both laboratories were combined and analyzed. The rate of weight loss in CsA treated rabbits was found to be a significant linear function of the dose. In addition, animal survival decreased and showed a dose-dependent linear relationship to CsA use. Grossly, all of the animals presented with full stomachs, incompletely digested, dry, hard, rabbit chow. Histopathology could not provide any insight into the mechanisms of this gross finding and remain unclear. The complete similarity of clinical and histopathological results in distant independent laboratories confirms the specificity of this CsA associated toxicity in the rabbit.

Animals↗
PubMed1990

High-dose recombinant human erythropoietin for treatment of anemia in myelodysplastic syndromes and paroxysmal nocturnal hemoglobinuria: a pilot study.

In a dose escalation study we tested the feasibility and tolerance of high-dose recombinant human erythropoietin (r-HuEPO) therapy in four patients with ineffective erythropoiesis due to myelodysplastic syndromes (MDS) or paroxysmal nocturnal hemoglobinuria (PNH). Recombinant human EPO was administered i.v. with an initial dose of 50 U/kg body weight (BW) three times per week. The dose was increased by steps of 25 or 50 U/kg bW with intervals of 1-4 weeks up to a maximum dose of 500 U/kg BW three times per week. All patients were treated as outpatients. Pre-study treatment with cyclosporin A and/or Danazol was continued in three patients. In one patient r-HuEPO was discontinued after 20 weeks because of relapse of severe aplastic anemia. No major side effects were observed even at the maximum dose. One patient with PNH showed an increase of hemoglobin from 89 to 139 g/liter that permitted monthly phlebotomies to reduce his iron overload. In one patient with MDS the reticulocyte count increased from 2.5 to 50 x 10(9)/liter, and the transfusion requirement decreased to 2 U every 3-4 weeks instead of every 2 weeks. Two patients did not complete the whole treatment period and showed no rise in reticulocyte count. We conclude that high dose r-HuEPO therapy is feasible in patients with anemia due to MDS or PNH. High-dose r-HuEPO appears to have some effect on anemia due to ineffective erythropoiesis in a subgroup of patients. Further studies are needed to identify potential responders and to define the optimal administration of r-HuEPO.

Adult↗
PubMed1990

Allogeneic bone marrow transplantation for leukemia in Europe: regional differences. Report from the Leukemia Working party of the European Group for Bone Marrow Transplantation.

The results of 1904 allogeneic HLA identical sibling donor bone marrow transplants performed in 52 European centers between 1979 and 1986 and reported to the EBMT leukemia registry were analysed by geographical location of the transplant. Patients were grouped into six regions: United Kingdom, Nordic Group, Benelux, France, Central Europe and Southern Europe. There were significant differences between these regions with respect to patient population and outcome. The relative proportion of the three major disease categories, stage and subtype of the diseases, graft-versus-host disease prevention methods, donor recipient sex combinations, age of the patient, year of the transplant and the time intervals from diagnosis to transplant, from diagnosis to first complete remission for acute leukemia and the time from first complete remission to the transplant varied from region to region. The analysis of outcome parameters showed a significant difference in relapse incidence from region to region. This influence of region was confirmed in a multivariate analysis and was independent of the other factors known to affect outcome. Leukemia-free survival and transplant-related mortality were not different. The reasons for these differences could not be explained by the data in the registry. We conclude that regional factors must be considered when bone marrow transplant data are compared and we postulate that pretransplant factors probably affect outcome more than was previously realized.

Adolescent↗
PubMed1989

[Therapy of thrombocytosis in myeloproliferative syndromes using recombinant interferon-alpha-2a].

In a prospective open study 16 consecutive patients with a myeloproliferative syndrome and thrombocytosis were treated with interferon (IFN) alpha-2a. 4 patients had polycythemia vera, 4 essential thrombocythemia, 3 myeloid metaplasia and 5 chronic granulocytic leukemia. Platelet counts decreased in all treated patients within 2 to 12 weeks from a median value of 1010 x 10(9)/l to 350 x 10(9)/l. No primary or secondary resistance was observed. The initial dose of IFN was 9 m U per day. After correction of the thrombocytosis, it was progressively reduced to a minimum dose of 3 m U per week. Despite the good platelet response to IFN, leukocytosis persisted in 3 patients and polycythemia in a further 3. Side effects and poor compliance required discontinuation of therapy in 6 patients. Special attention is focused on the follow-up in 6 patients who have been treated for more than 15 months.

Adult↗