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Biomedical subjects

B Osterwalder

Publications and source records attributed to B Osterwalder.

69 records · Page 4Linked to original sources
PubMed1983

Cyclosporine in human bone marrow transplantation. Serum concentration, graft-versus-host disease, and nephrotoxicity.

Serum concentrations of cyclosporine were studied in 42 patients given cyclosporine for the prevention of graft-versus-host-disease (GVHD) following allogeneic bone marrow transplantation (BMT). Serum trough levels for cyclosporine were determined in each patient at least once weekly during the first 3 months and were compared with the occurrence of GVHD and with nephrotoxicity. Cyclosporine was given as 20 mg/kg i.m. or as a 24-hr infusion for the first 5-7 days. This was followed by a single daily oral dose of 12.5 mg/kg for 6 months. Cyclosporine was then gradually reduced and stopped after one year. After a median observation period of 2 years 25 of the 42 patients (59%) are alive. Twenty six patients (62%) developed GVHD, which was stage II or more in 11 (26%) and fatal in 2 patients (5%). Five patients developed GVHD 6-8 weeks after withdrawal of cyclosporine one year after BMT. All patients improved after restarting cyclosporine. No correlation between cyclosporine serum concentration and GVHD was observed, but patients with GVHD had greater fluctuations of their serum trough levels. Serum creatinine increased in all patients soon after BMT and was correlated with cyclosporine serum concentration during the first month. Serum creatinine, however, rose further despite lower cyclosporine concentrations in the second month. These results show that cyclosporine effectively reduces the severity, but not the incidence, of GVHD suggesting that there is a subset of cells resistant to cyclosporine. The therapeutic range, however, between high doses (which are often associated with nephrotoxicity) and the minimal effective dose of cyclosporine, has yet to be defined.

Adolescent↗
PubMed1983

Immunologic reactivity in marrow graft recipients receiving cyclosporine to prevent graft-versus-host disease.

In vitro and in vivo immunologic parameters were determined in 26 patients treated continuously with cyclosporine to prevent graft-versus-host-disease (GVHD) after allogeneic bone marrow transplantation (BMT) for acute and chronic leukemia and for aplastic anemia. A group of 18 patients was tested 6 months after BMT and another group of 10 patients was tested after one year. At 6 months after BMT, 94% of the patients had normal serum IgG and IgM levels, whereas at one year 29% of them had low IgA levels. The proportion of patients with normal lymphocyte responses in vitro at 6 months after BMT was 69% and 76% for the responses to concanavalin A and to soluble antigens; 75% and 53% for the responses to allogeneic cells and pokeweed mitogen, respectively; and 89% for the response to phytohemagglutinin. All but one were able to generate suppressor cells upon con A stimulation. At one year after the graft, only one patient had demonstrable multiple abnormalities in in vitro tests. Skin test reactivity at one year was comparable to pre-graft reactivity. After BMT a lymphopenia persisted for 6 months. The rate of infectious complications was high during the first 3 months after BMT, and it diminished progressively as immune functions returned to normal. Infection was the cause of death in two cases (one disseminated cytomegalovirus infection and one septicemia). GHVD occurred in 12 patients; in nine of them the disease was transient and mild, only 1 patient developed severe chronic GVHD. Acute GVHD did not influence the tempo of immunologic reconstitution. In comparison to other studies, it seems that cyclosporine does not delay immune restoration, or increase morbidity from infection, while preventing GVHD and its complications efficiently.

Anemia, Aplastic↗
PubMed1983

Bone marrow graft versus ALG in patients with aplastic anaemia.

Eighty-six successive patients with severe aplastic anaemia were admitted to this hospital between January 1976 and October 1982. They were treated and evaluated in a prospective study according to one protocol. 26 patients with an HLA identical sibling underwent bone marrow transplantation. Overall survival calculated according to Kaplan and Meier in this group is 47%, 60 patients without an HLA identical sibling were given antilymphocyte globulin with or without an infusion of HLA-haploidentical marrow. All these 60 patients received low dose androgens after the procedure. In this study the marrow infusion did not significantly improve the results and overall survival was 74% compared to 70% in patients receiving only antilymphocyte globulin and androgens. In a current pilot study combining ALG and high dose prednisone we were able to further increase remission rates. Between HLA-identical siblings we improved the results of marrow transplants significantly by the use of cyclosporin-A instead of methotrexate for prophylaxis against GvHD.

Adolescent↗
PubMed1983

Delayed alloimmunization using random single donor platelet transfusions: a prospective study in thrombocytopenic patients with acute leukemia.

A randomized study was performed in 54 thrombocytopenic patients with acute leukemia. Alloimmunization of recipients of random multiple-donor platelet concentrates (MD group) was compared to that of patients receiving random single-donor platelets (SD group). In the SD patients, formation of alloantibodies (mostly anti-HLA) occurred less frequently (p less than 0.002), after a longer time period (p less than 0.002), and after a higher number of transfusions (p less than 0.005) as compared to MD patients. SD patients also became refractory to random platelets less frequently (p less than 0.005), after a longer time period, and after a higher number of transfusions (p less than 0.02). In SD patients, the increments after the first and the last transfusion were in the same range, whereas in MD patients, the 1-hr (p less than 0.001) and the 24-hr (p less than 0.025) increments decreased from the first to the last transfusion. Thus, the use of random SD platelet transfusions postponed alloimmunization.

Acute Disease↗
PubMed1982

Allogeneic marrow transplantation for chronic granulocytic leukemia.

Six patients with Philadelphia-chromosome (Ph' +)-positive chronic granulocytic leukemia were transplanted from their HLA-identical siblings after conditioning with cyclophosphamide and 1'000 rad total body irradiation. All received cyclosporin-A for prophylaxis of Graft-versus-Host disease. All patients showed prompt engraftment and all are cytogenetically and clinically in complete remission. Two patients had transient mild signs of Graft-versus-Host-disease and one patient had unilateral facial nerve paresis of unknown origin. All are ambulatory and well 6-18 months (median 10 months) after transplantation.

Adolescent↗
PubMed1981

[Clinical and therapeutic study of a group of 217 patients with intestinal giardiasis and amebiasis].

In 15 months of the years 1979-1980, 158 patients with giardiasis and 69 patients with intestinal amebiasis were diagnosed and treated in the outpatient department of the Swiss Tropical Institute. Repeated examination of merthiolate-iodine-formol-fixed stools was the method of choice for detecting intestinal protozoa. Parasitological investigation of duodenal fluid (Enterotest) was less effective. Fewer than 30% of the cases were symptomatic, usually mentioning diarrhea (73-85%) or abdominal discomfort (20-44%). Treatment was by ornidazole single dose (2 g in adults; 40 mg/kg in children) for asymptomatic cases and a five-day treatment schedule (2 X 500 mg/day in adults, 20 mg/day in children) for symptomatic cases. In amebiasis a luminal amebicide (diloxanide furoate) was prescribed in all instances after the first stool examination. Parasitological cure rates were excellent (95%) in all cases of giardiasis but only 59 and 65% respectively in cases of asymptomatic and symptomatic amebiasis. Drug tolerance was excellent. Ornidazole is the drug of choice for all forms of giardiasis, even in a single dose. As a luminal amebicide, however, its efficacy is not superior to other nitroimidazole derivatives.

Drug Administration Schedule↗
PubMed1981

[New development in clinical bone marrow transplantation in leukemia].

39 clinical bone marrow transplants (BMT) for leukemia are described. In a historical control series of 18 patients in whom BMT was performed after all chemotherapeutic resources had been exhausted, there is only 1 long-term survivor (5.5%), 8 patients died from GvH reaction, 6 from interstitial pneumonia and 3 from recurrent leukemia. Since 1979 an attempt has been made to transplant patients under optimal conditions (1st complete remission) and cyclosporin-A (CyA) has been used for prophylaxis of GvH reaction instead of MTX. 11 patients were transplanted according to our original proposal (AML and ALL in first remission, CML in chronic phase): 10 have survived without evidence of leukemia (91%), 1 AML died in relapse. 10 patients were grafted in second or later remissions or early relapse: 5 have leukemia-free survival (50%), 1 is living with a relapse. In this group 3 deaths were due to recurrent leukemia and 1 to CMV-infection. In our experience BMT under optimal circumstances does not involve a risk of early mortality and the chances of recurrent leukemia are reduced. Severe or chronic GvH reaction is not seen under CyA. BMT is the treatment of choice for patients with histocompatible sibling donors.

Bone Marrow Transplantation↗
PubMed1981

[Treatment of severe aplastic anemia].

58 patients with severe aplastic anemia (SAA) were treated and evaluated in a prospective study either by bone marrow transplantation (BMT) or by antilymphocyte globulin (ALG). 19 patients were treated with BMT; 9 are still alive 6 months to 5 years after BMT (47%). 39 patients were treated with ALG; 28 are alive 5 months to 5 years after ALG (72%). 24 of these 28 are self-sustaining and in remission. The results show that treatment with ALG is probably superior to treatment with BMT, and also demonstrate that most patients with SAA have a pool of hematopoietic stem cells able to repopulate the marrow after this type of treatment.

Adolescent↗
PubMed1981

Treatment of severe aplastic anaemia with antilymphocyte globulin or bone-marrow transplantation.

Fifty-three patients with severe aplastic anaemia were admitted to this hospital between January 1976 and June 1980, of whom three arrived in terminal condition and died before treatment for their basic disease could be given. Thus 50 patients were treated and evaluated in a prospective study according to one protocol. Eighteen patients with an HLA-identical sibling underwent bone-marrow transplantation with the aim of achieving haematopoietic chimerism. Thirty-two patients without an HLA-identical sibling were given antilymphocyte globulin with or without an infusion of HLA-haplotype-identical marrow. All these 32 patients received low-dose androgens after the procedure. In the first group eight patients (44%) survived. In the two other groups, 22 patients survived (69%), of whom 20 were completely self-sustaining (63%). Engraftment and graft-versus-host disease did not occur in the group who received antilymphocyte globulin and haploidentical marrow, and the haematopoietic reconstitutions in these patients were all autologous. These results confirm the efficacy of antilymphocyte globulin in the treatment of severe aplastic anaemia and show that such treatment is at least as good as bone-marrow transplantation. Its mechanism of action remains unknown, but most patients with aplastic anaemia have a pool of haematopoietic stem cells able to repopulate the marrow after this type of treatment.

Adolescent↗
PubMed1980

[Experience with intensive plasma exchange].

Experience with a total of 49 plasma exchanges in 14 patients is reported. All exchanges were performed with the Aminco cellseparator in an attempt to remove documented or suspected antibodies completely. Indications were ABO-barrier before bone marrow-transplantation (6), acute rejection following renal transplantation (3), autoimmune diseases (3), Moschowitz disease, antithrombocytic antibodies and hepatic coma (1 each). The technique was modified to make it possible routinely to exchange 121 of plasma in 4 hours with no major untoward side effects even in anuric or thrombopenic patients. Complete removal of circulating antibodies was possible and often followed by impressive clinical benefit.

ABO Blood-Group System↗
PubMed1976

[Morphological studies on the human heart conduction system].

An attempt has been made to demonstrate morphological equivalents of electrocardiographically determined conduction disturbances in the human heart. In 50% of our cases an authentic morphological change was found. In 25% the correlation remained doubtful, and in another 25% there was no connection. The highest coincidence was found in chronic left bundle branch block and in dissecting aneurysms causing hemopericardium. The correlation between function and morphology is very loose in patients who have undergone cardiac surgery. Etiology is discussed only marginally; ischemia is the predominant feature.

Aged↗
PubMedDate not supplied

All-trans retinoic acid as an alternative to chemotherapy in the treatment of acute promyelocytic leukemia.

A 12-year-old girl with acute promyelocytic leukemia has been treated with conventional chemotherapy. The patient remained in complete remission for a year when the first bone marrow relapse occurred. Since reinduction chemotherapy was rejected by the parents, an alternative treatment with oral all-trans retinoic acid was administered. A second complete remission was achieved within 100 days. After 14 months a second bone marrow relapse occurred. All-trans retinoic acid and the combination with interferon-alpha failed.

Child↗