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E Signer

Publications and source records attributed to E Signer.

At least 19 recordsLinked to original sources
PubMed1992

[Swiss Register for unrelated bone marrow donors: preliminary results].

Bone marrow transplantation from the unrelated volunteer donor is today a realistic possibility for patients lacking an HLA-identical family donor. In 1988, the Swiss Unrelated Bone Marrow Donor Registry was founded to coordinate such bone marrow transplants and create the Swiss volunteer donor registry. Thus for a search has been initiated for 71 patients and 16 transplants have been performed. Donor and recipient were HLA-A-, -B- identical by serology and HLA-Dr-identical by DNA-oligotyping. 10 of the 16 patients are alive without signs of basic disease 2 weeks to 2 years and 4 months after the transplant. These results illustrate that unrelated donor transplantation, using careful selection criteria, is a realistic new therapeutic modality.

Adolescent↗
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

Purification and properties of DNA topoisomerase I from broccoli.

We have purified a topoisomerase activity from broccoli (Brassica oleracea var. italica) to near homogeneity. The enzyme is an 80 kDa monomer as judged by gel filtration chromatography and SDS gel electrophoresis, though it may represent a proteolytic fragment of a larger protein. The enzyme is capable of removing both negative and positive supercoils in steps of one, does not absolutely require Mg2+, is only very weakly stimulated by NaCl, is inhibited by camptothecin, and cross-reacts with an antibody directed against human DNA topoisomerase I. These properties identify the enzyme as a eukaryotic type I topoisomerase.

Blotting, Western↗
PubMed1992

Occurrence of large granular lymphocytes and natural killer cells in the epithelium of the gut distinguishes two different coeliac diseases.

In a longterm study, we have divided coeliac disease into two distinct entities (abortive and permanent) based on the occurrence of large granular lymphocytes and natural killer cells within the epithelium of the gut. The natural killer and large granular lymphocytes cells were characterised by either immunohistochemical or phase contrast microscopical procedures on the initial biopsies from 15 children with coeliac disease. They were compared with seven individuals with partial villus atrophy and eight with normal villous morphology. Although the histological findings were similar in the initial biopsies of all patients with coeliac disease, the patients with permanent coeliac disease had a significantly lower number (0.41(0.61)cells/mm2) of large granular lymphocytes and natural killer cells compared with those patients with abortive coeliac disease (11.93 (6.23) cells/mm2). Those in the permanent group developed a significantly more pronounced flat mucosa after gluten challenge or provocation compared with the abortive group and had to remain on a strict gluten free diet in contrast with those in the abortive group. Thus, the occurrence of intraepithelial large granular lymphocytes and natural killer cells characterises two distinctly different coeliac diseases. Based on our results neither the histological evaluation of the biopsy nor the utilisation of the revised European Society for Paediatric Gastroenterology and Nutrition (ESPGAN) Criteria are adequate in diagnosing the two types of coeliac disease.

Celiac Disease↗
PubMed1991

[Plasma cell granuloma of the lung].

Isolated primary tumors of the lung are rarely seen in childhood and are benign in one third of the patients. Plasma cell granulomas represent the most common benign tumor of the lung in this age group. Histologically, the tumor is characterized by the various components of a chronic inflammation or granulation tissue. Frozen sections can pose difficulties in the differentiation between a malignant and benign process. In view of the case history of our patient we set out to demonstrate that a knowledge of the clinical picture and a correct interpretation of associated laboratory findings facilitate diagnosis. To our knowledge we describe for the first time the ultrastructural findings of so-called "microtubule-reticular structures" giving further evidence of the inflammatory origin of this lesion.

Child↗
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↗
PubMed1989

Bone marrow transplantation in Basel: single center experience from 1973 to 1989.

Bone marrow transplantation with a small to medium-sized single hospital team is feasible. It leads to results similar to those observed at large centers and with the same major risk factors: age, stage of the disease at the time of transplant, degree of histocompatibility, graft-versus-host disease prevention method, and selection. A single small to medium-sized center cannot conduct prospective randomized studies but it can pioneer new concepts. Bone marrow transplantation today offers a good choice for patients suffering from otherwise lethal bone marrow diseases. These include severe aplastic anemia, acute leukemias, chronic myeloid and chronic lymphoid leukemia, myelodysplastic syndrome, and congenital disorders. Changes in outcome are due to innovative steps, such as the introduction of CsA for GvHD prevention. In addition they are certainly influenced by unrecognized changes in the patient selection process.

Anemia, Aplastic↗
PubMed1988

[Late complications in patients with aplastic anemia].

Of 145 patients with severe aplastic anemia (SAA) treated in Basel from 1976 to 1987, 34 underwent bone marrow transplantation (BMT) and 111 received ALG therapy. We have analyzed the incidence of late complications in both groups of patients. 34 patients treated with ALG developed a hematological complication, 10 a myelodysplastic syndrome (MDS) and 18 paroxysmal nocturnal hemoglobinuria (PNH) associated with clinical symptoms in 12. Two patients had both MDS and PNH. Eight suffered relapse of SAA. After BMT neither of these complications occurred. Most of the non-hematological problems were associated with therapy. In the ALG group androgens were responsible for impotence and gynecomastia in men, deep voice in women and liver tumors in 4 patients. Four other patients developed aseptic necrosis of the hip and one carcinoma of the breast. The most severe late complication after BMT was chronic graft-versus-host disease (GvHD), occurring in patients still receiving methotrexate for prophylaxis of GvHD.

Anemia, Aplastic↗
PubMed1988

Mutation analysis of the N-ras proto-oncogene in active and remission phase of human acute leukemias.

DNA isolated from blood or bone-marrow samples from 18 patients with acute non-lymphocytic leukemia (ANLL) and 14 patients with acute lymphocytic leukemia (ALL) was analyzed for the presence of mutations in the N-ras gene. Using synthetic oligonucleotide probes we detected mutations in 5 cases of ANLL; 4 GGT----GAT transitions in codon 12 and one CAA----AAA transversion in codon 61. One case exhibited homozygosity for the mutation. No mutations could be detected at these codons in the DNA of the 14 ALL patients. In a follow-up study with 3 of the above 5 patients, the mutation could no longer be detected in 2 cases following successful induction of clinical remission by chemotherapy. However, the mutated N-ras persisted in one patient who did not achieve remission. We show that oligonucleotide hybridization is a sensitive assay for the detection of N-ras point mutations, which in ANLL could be used to follow the fate of the leukemic clone during (and after) therapy.

Acute Disease↗
PubMed1988

[Cervical thymic cyst in childhood].

In three children (2, 4 and 10 years of age) a cervical thymic cyst was removed. We found multilocular cysts with xanthochromic luminal fluid covered with a fibrous capsule. Histological features are lymphatic follicles, partly atrophic, as well as regular thymic tissue with cortex, marrow and Hassall's corpuscles.

Child↗
PubMed1988

Repair of UV-induced DNA damage in aplastic anaemia: changes after treatment with antilymphocyte globulin (ALG).

The extent of DNA-repair induced by UV-C irradiation was measured in peripheral unstimulated lymphocytes of 24 patients with aplastic anaemia at different stages of disease and compared with the results obtained in 92 controls. As parameter of the DNA-repair synthesis, the incorporation of (3H)thymidine in the presence of 2 mmol/l hydroxyurea (HU) was taken. Of 19 patients tested after treatment with antilymphocyte globulin (ALG), 5 were in complete autologous haemopoietic remission, defined as greater than 1000 granulocytes/mm3, greater than 100,000 platelets/mm3 and a nontransfused haemoglobin value greater than 10 g%. 14 patients were in partial remission, defined as improvement of haemopoietic function, not meeting the criteria for complete remission. 4/5 patients in complete remission had normal DNA-repair synthesis, compared to 4/14 patients in partial remission. In 92 controls, a normal level was found in 70 cases. In 4/5 patients examined at diagnosis and at various intervals after ALG-treatment, DNA-repair synthesis was low at diagnosis. It increased after therapy and paralleled improvement of haemopoietic function to some extent. It is suggested that in aplastic anaemia there are different populations of lymphocytes with differing DNA-repair capacity; ALG treatment seems to favour expansion of the normal population, which is associated with improvement of haemopoietic function.

Adolescent↗
PubMed1987

A comparison between ALG and bone marrow transplantation in treatment of severe aplastic anemia.

One hundred patients with severe aplastic anemia were treated and evaluated in a prospective study at our hospital between January 1976 and October 1983. 28 patients had a HLA-identical sibling donor and were treated with bone marrow transplantation. 72 patients without a HLA-identical sibling donor were given antilymphocyte globulin followed by oral low dose androgen therapy. One and a half years to nine years after treatment 13 patients (46%) survive in the transplant group and 53 patients (74%) survive in the second group. All except one in the second group have self-sustaining hematopoiesis without need for transfusions. There is one major difference between the two therapies. Marrow transplantation restores bone marrow function completely and no late hematological complications have been seen in this group. The majority of patients treated with antilymphocyte globulin in contrast have residual abnormalities of hemopoiesis: macrocytosis, mild granulocytopenia and mild thrombocytopenia. Relapse (11 of 72 patients) and clonal hematological disorders, such as paroxysmal nocturnal hemoglobinuria (4 patients) and leukemia (one patient) can occur years after complete bone marrow reconstitution with antilymphocyte globulin. These late disorders are of concern. In spite of this we conclude that antilymphocyte globulin treatment is an effective therapy with low early mortality and morbidity and a high chance for a long sustained remission. Results are better or at least equivalent to bone marrow transplantation and patients with donors should be given the option of transplantation or antilymphocyte globulin.

Anemia, Aplastic↗