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S Brugger

Publications and source records attributed to S Brugger.

At least 19 recordsLinked to original sources
PubMed2001

Long-term clinical and molecular remission after allogeneic stem cell transplantation (SCT) in patients with poor prognosis non-Hodgkin's lymphoma.

From 1987 to 1999 35 patients with poor prognosis non-Hodgkin's lymphoma (NHL) underwent allogeneic stem cell transplantation (SCT) at the University Hospitals of Vienna and Graz. Initial biopsy specimens were reclassified according to the Revised European-American Classification of Lymphoid Neoplasms (REAL). All patients surviving 28 days engrafted. Twenty-eight of them (93%) attained clinical remission. At the last follow-up 14 patients were alive and disease-free at a median of 5.0 (range, 2.3-12.9) years after allogeneic SCT. The actuarial overall survival is 35%. Five patients relapsed 1.8 to 27.6 months after transplant, the probability of relapse is 23%. Of the 21 deaths following SCT, seven were due to relapse/refractory disease and 14 due to transplant-related causes. The probability of treatment-related mortality is 48%. After SCT, minimal residual disease (MRD) was monitored by polymerase chain reaction (PCR) in seven patients with a BCL-2/IgH translocation and in 13 with a clonal immunoglobulin heavy chain (IgH) rearrangement. All 20 patients attained clinical remission rapidly and converted to PCR negativity. In the follow-up nine of these patients are in long-term clinical and molecular remission, six PCR-negative patients died of transplant-related causes and five patients relapsed. In summary, allogeneic stem cell transplantation has a curative potential for patients with refractory and recurrent non-Hodgkin's lymphoma. In our series long-term disease-free survival was associated with molecular disease eradication after SCT. Treatment-related mortality rate was high, thus earlier referral of selected patients to allogeneic SCT should be considered.

Adult↗
PubMed1999

Long-term follow-up of patients after related- and unrelated-donor bone marrow transplantation for chronic myelogenous leukemia.

Between January 1983 and December 1997, 88 patients (36 female, 52 male, median age 37 years, range 19-57) with chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation (BMT) at the University Hospital of Vienna. Sixty patients were in chronic phase, 18 in accelerated phase, and ten in blast crisis. Marrow donors were HLA-identical siblings for 64 patients (BM 58, PBSC 6), 2-antigen-mismatched related donors (RD) for two, HLA-identical unrelated donors (URD) for 17, and 1-antigen-mismatched URD for five. The median time from diagnosis to BMT was 22 months (range 2-91), and 63 patients had received prior interferon (IFN)-alpha therapy, 46 (73%) for more than 6 months. Conditioning therapy consisted of cyclophosphamide (CY) and total body irradiation (TBI) in 71 patients and CY and busulfan (BU) in 16. One patient received etoposide and TBI. For graft-versus-host disease (GVHD) prophylaxis methotrexate (MTX) was given to 12 patients, MTX and cyclosporin A (CSA) to 67, CSA alone to four, and CSA and methylprednisolone to five. Durable engraftment was documented in 80 of 82 patients (98%). As of December 31, 1997, 52 patients (59%) were alive, 38 (58%) after sibling transplantation with a median observation time of 73 months and 14 (64%) after URD transplantation with a median observation time of 12 months. Probability of overall survival is 59%, for patients undergoing transplantation in chronic phase and 44% for patients undergoing transplantation in advanced stage CML. Probability of disease-free survival (DFS) after sibling and URD BMT is 55% and 59%, respectively. Ten patients (12%) experienced relapse of CML. Transplant-related mortality was 32% both after RD and after URD transplantation. Acute GVHD occurred in 53 of 80 evaluable patients (66%), consisting of grade III or IV in 14 patients (18%). Chronic GVHD developed in 40 of 63 eligible patients (63%), including extensive disease in 26 patients (41%). Thus, sibling and URD BMT offer high cure rates with acceptable toxicity to patients with CML.

Acute Disease↗
PubMed1999

Low transplant-related mortality in patients receiving unrelated donor marrow grafts for leukemia.

Transplantation with unrelated donor (UD) marrow has been shown to potentially cure patients with leukemia. Between January 1991 and April 1998, 54 patients with leukemia have received an UD BMT at our institution. Five patients received their UD BMT as a second transplant after a preceding autologous or syngeneic BMT and were excluded from further analysis. Forty-nine patients with leukemia (acute leukemia n = 26; CML n = 23) and a median age of 36 years (range 19-51) were analyzed. For conditioning, all patients received a combination of fractionated TBI and CY. GVHD prophylaxis consisted of MTX and CsA in all patients. As of 30 April 1998, 27 of 49 (55%) patients survive after a median observation time of 18 months. The probability of overall survival for standard risk and high risk patients is 54% and 31% (P = 0.05). Probability of transplant-related mortality (TRM) is 27%, 24% in standard risk and 31% in high risk patients (P = 0.44). Patients younger than 40 years (n = 33) had a similar TRM as patients 40 years and older (n = 16). The probability of relapse is 41% for the whole group, 29% for standard risk and 55% for high risk pts (P<0.05). Our data confirm that UD BMT is an effective treatment for patients with leukemia. TRM is almost similar to related sibling BMT, most probably due to improvements in HLA typing technology, conditioning regimen and supportive patient care.

Adult↗
PubMed1998

Subdural hygromas after bone marrow transplantation: results of a prospective study.

BACKGROUND: Subdural hygromas after bone marrow transplantation (BMT) have been occasionally found in patients with persisting headache and vomiting. We assessed the incidence of subdural hygromas after BMT and tried to define possible risk factors associated with this complication. METHODS: Fifty bone marrow graft recipients surviving more than 30 days were consecutively enrolled into a prospective study. Cranial CT scans were performed before and 30 days after BMT. Clinical data and symptoms were recorded daily during the first 30 days after BMT. In patients with subdural hygromas, a magnetic resonance imaging scan and monthly follow-up cranial computed tomography scans were performed until fluid collections had resolved completely. RESULTS: In 9 of the 50 patients (18%) who survived 30 days after transplantation, newly acquired subdural hygromas were found. Patients with hygromas suffered significantly longer and more severely from headache and vomiting (P=0.01). Application of intrathecal methotrexate and arterial hypertension occurred significantly more often in patients with hygromas (P=0.01). In a stepwise logistic regression model, arterial hypertension and intrathecal methotrexate application were the only independent risk factors for the development of hygromas. Monthly follow-up cranial computed tomography scans showed that all hygromas resolved completely after a median of 60 days after diagnosis (range: 30-120 days). CONCLUSIONS: Subdural hygromas are a frequent complication after BMT within the first 30 days after transplantation. They are reversible and disappear within 2-3 months. The need for routine application of intrathecal methotrexate in standard risk leukemia patients should be critically addressed. Furthermore, close monitoring of blood pressure and immediate antihypertensive therapy might contribute to avoid formation of subdural hygromas.

Adolescent↗
PubMed1998

ICV administration of CRF blocker (CRF9-41 delta helical) reduces morphine withdrawal in rats.

1. The effects of CRF9-41 delta helical on morphine withdrawal signs in rats were studied. 2. Intracerebroventricular administration of CRF9-41 delta helical 5 at 10 micrograms/kg reduced central and peripheral symptoms of the withdrawal syndrome, such as ptosis, jumping, wet dog shakes and teeth chattering; other signs remained unchanged. The effect were not dose dependent. 3. The hypothermi characteristic of the Withdrawal syndrome was reduced by CRF9-41 delta helical. 4. These results suggest that the hypothalamo pituitary adrenal(HPA) axis play an important role in the morphine withdrawal syndrome in rats.

Animals↗
PubMed1998

Elevated numbers of reticulated platelets in hyperthyroidism: direct evidence for an increase of thrombopoiesis.

We studied thrombopoietic activity in hyperthyroidism by determination of reticulated platelet counts. At the time of hyperthyroidism 14/15 patients had higher reticulated platelets than after achievement of euthyroidism (P<0.001). There was no difference in peripheral platelet counts and mean platelet volumes at the time of hyperthyroidism when compared to euthyroidism. Three patients had pan- and auto-reactive platelet antibodies during hyperthyroidism. These antibodies were directed against GPIIb/IIIa in two patients and against GPIb/IX in one patient. Our findings provide direct evidence that hyperthyroidism is associated with increased platelet production, as reflected by an increase in reticulated platelets.

Adult↗
PubMed1998

Kinetics of circulating selectin levels during bone marrow aplasia.

We have studied the kinetics of plasma levels of circulating (c)selectins in 8 patients undergoing bone marrow or stem cell transplantation to gain estimates for the distribution and half-life of (c)selectins and to potentially identify an endothelial source of cP-selectin in patients who are deprived of platelets and megakaryocytes. Blood was sampled just before conditioning treatment and immediately after, at 2 occasions under bone marrow aplasia (1 and 2 wk after BMT), on 2 separate days (3-8 d apart) before and at 60 min after platelet transfusion, and 30-72 d after BMT. All (c)selectins showed a strikingly parallel decrease during bone marrow aplasia: cP-selectin decreased by a median of 70% (range: 59-95%), cE-selectin by 63% (range: 27-78%), and cL-selectin by 75% (range: 66-90%) compared to baseline (p=0.012 for all comparisons). Estimates for plasma half-lives of all (c)selectins were obtained from individual time vs. concentration profiles of the maximal decreases and ranged from 2 to 4 d. cP-selectin increased by 23% (p=0.003), cE-selectin by 5% (p=0.041) and cL-selectin by 19% (p=0.009) 1 h after the platelet transfusions. Based on these results the calculated volume of distribution (Vd) of transfused (c)selectins was 2.5-fold higher than the plasma volume, which supports the concept of the in-vivo expression of binding sites, i.e. ligands, for cE-selectin and cL-selectin. In summary, while our study cannot provide any evidence for endothelial cells as a source of cP-selectin, we have found for the first time evidence for the existence of ligands for soluble cE-selectin and cL-selectin in humans.

Adult↗
PubMed1998

Competitive CBFbeta/MYH11 reverse-transcriptase polymerase chain reaction for quantitative assessment of minimal residual disease during postremission therapy in acute myeloid leukemia with inversion(16): a pilot study.

PURPOSE: (1) Quantification of minimal residual disease (MRD) by competitive CBFbeta/MYH11 reverse-transcriptase polymerase chain reaction (RT-PCR) in patients with acute myeloid leukemia (AML) and inversion(16) [inv(16)] during postremission therapy, (2) comparison of this method with conventional two-step RT-PCR, and (3) evaluation of a potential prognostic value. PATIENTS AND METHODS: MRD of six consecutive adult patients with AML and inv(16)(p13;q22) or t(16;16)(p13;q22) who entered complete remission (CR) was monitored by competitive CBFbeta/MYH11 RT-PCR in their bone marrow (BM) during postremission therapy with high-dose cytarabine (HiDAC) or after BM transplantation with a matched unrelated-donor marrow (MUD-BMT) during an observation period of 4.5 to 27 months after initiation of treatment. RESULTS: Competitive PCR showed a gradual decline by at least 4 orders of magnitude after 7 to 9 months in patients in continuous CR (CCR), while one patient who relapsed after 13.5 months only achieved a reduction by 2 orders of magnitude at the end of consolidation therapy. A rapid decrease below the detection limit was observed within 1 month in two patients after MUD-BMT. A temporary reappearance of molecular MRD was observed in these patients during immunosuppression for graft-versus-host disease (GvHD). After reduction of immunosuppression, the level of MRD dropped again below the PCR detection limit. Molecular monitoring by conventional two-step RT-PCR yielded comparable results only when multiple assays per time point were performed, while single-assay RT-PCR gave misleading results. CONCLUSION: Competitive RT-PCR is a valuable tool for molecular monitoring during postremission chemotherapy, as well as after BMT.

Adolescent↗
PubMed1998

Long term follow up after allogeneic stem cell transplantation for chronic myelogenous leukemia.

Between January 1983 and July 1997, 83 patients (35 female, 48 male) with a median age of 37 (19-57) years with chronic myelogenous leukemia (CML) were admitted for bone marrow transplantation (BMT) at the University hospital of Vienna. Fifty-six patients were in chronic phase, 17 in accelerated and 10 had blast crisis. Marrow donors were: HLA-identical siblings in 62 patients, 2-antigen mismatched related donor in 2, HLA-identical unrelated donors (MUD) in 17 and 1-antigen mismatched unrelated donor in 2 patients. The median time from diagnosis to BMT was 22 (2-91) months. Conditioning therapy consisted of cyclophosphamide (CY) and total body irradiation or CY and busulfan. For graft-versus-host disease (GVHD) prophylaxis methotrexate (MTX) alone, MTX and cyclosporine A (CSA), CSA alone or CSA and methylprednisone were given. Durable engraftment was documented in 75 of 77 patients (97%). As of July 31, 1997 48 patients are alive (58%), 36 (56%) after sibling transplantation with a median observation time of 77 months and 12 (63%) after MUD transplantation with a median observation time of 13 months. Overall survival for patients in chronic phase (CP) at time of BMT is 64%, 53% for patients in acceleration and 30% for patients in blast crisis (BC). Disease-free survival (DFS) after sibling BMT and unrelated donor transplantation is 53% and 58%, respectively. Ten patients (12%) experienced relapse of CML. Transplant-related mortality was 33% after sibling and 32% after MUD transplantation. Thus, sibling and unrelated donor BMT offer high cure rates with acceptable toxicity to patients with CML.

Adult↗
PubMed1997

Genetic and biochemical analysis of the transmembrane domain of Arabidopsis 3-hydroxy-3-methylglutaryl coenzyme A reductase.

We have examined the amino terminal membrane anchoring domain of Arabidopsis thaliana 3-hydroxy-3-methylglutaryl coenzyme A reductase (Hmg1p), a key enzyme of the isoprenoid biosynthetic pathway. Using both in vitro and in vivo approaches, we have analyzed a series of recombinant derivatives to identify key structural elements which play a role in defining Hmg1p transmembrane topology. Based on our results, we have proposed a topological model for Hmg1p in which the enzyme spans the lipid bilayer twice. We have shown the two transmembrane segments, designated TMS1 and TMS2, to be structurally and functionally inequivalent in their ability to direct the targeting and orientation of reporter proteins. Furthermore, we provide evidence indicating both the extreme amino terminal end and carboxyl terminal domain of the protein reside in the cytosol. This model therefore provides a key basis for the future examination of the role of the transmembrane domain in the targeting and regulation of Hmg1p in plant cells.

Algorithms↗
PubMed1997

Excellent long-term survival after allogeneic marrow transplantation in patients with severe aplastic anemia.

Between 1982 and 1996, 20 patients (10 male, 10 female) with severe aplastic anemia (SAA) with a median age of 25 years (17-37 years), received grafts from an HLA-identical sibling (n = 17), HLA-identical unrelated donor (n = 2) or identical twin (n = 1). The median time from diagnosis to marrow transplantation (BMT) was 15 months (range 1-96 months). More than half of the patients had received more than 10 units of red blood cells or platelet transfusions prior to BMT. Pretransplant immunosuppression consisted of cyclophosphamide (CY) alone (n = 10), CY in combination with total body irradiation (n = 8), and CY and antithymocyte globulin (n = 2). For graft-versus-host disease (GVHD) prophylaxis methotrexate (MTX) alone (n = 9) or MTX with cyclosporin A (n = 10) were given. One patient died on day 18 after marrow grafting due to infection; all other patients had complete and sustained engraftment (95%). Eight patients developed acute GVHD (42%), nine patients chronic GVHD (53%) including four with extensive disease manifestation. One patient experienced a secondary malignancy 11 years after BMT. Eighteen patients followed for a median of 9.45 years (0.42-14.7 years) have sustained hematological reconstitution and are alive and well with a Karnofsky performance score of at least 90%. Thus, excellent long-term survival and low morbidity make allogeneic or syngeneic BMT the treatment of choice for younger patients with severe aplastic anemia.

Adolescent↗
PubMed1997

Percutaneous nonangiographic insertion of Hickman catheters in marrow transplant recipients by anesthesiologists and intensivists.

Long-term central venous lines for chronic hemoaccess are usually inserted in the operating theater under local or general anesthesia or in interventional radiology suites using fluoroscopic technique. In a prospective study we determined the feasibility of percutaneous insertion of Hickman catheters without fluoroscopic control by anesthesiologists and intensivists in the setting of an intensive care unit. Fifty-four Hickman catheters were placed in 53 consecutive patients with hematological disorders and/or neoplastic diseases undergoing allogeneic or autologous bone marrow transplantation (BMT) or buffy coat therapy. There were no major complications. The mean time for insertion was 35 min. The median life span of catheters was 70 days (range 3-214). Twenty-six catheters were electively removed; six remained functioning in situ at the end of the study. For 3333 catheter days (1471 days in hospital and 1862 days at domiciliary care), six catheters were removed because of mechanical complications (inadvertent dislodgement, leak, secondary migration) and 14 because of suspected or documented infection. We conclude that percutaneous nonangiographic insertion of Hickman catheters by anesthesiologists minimizes technical expenditure and is at least as effective as surgical or radiological techniques. The rate of clinically important complications is acceptable.

Adolescent↗
PubMed1997

Immunohistochemistry with monoclonal antibody against Candida albicans mannan antigen demonstrates cutaneous Candida granulomas as evidence of Candida sepsis in an immunosuppressed host.

We report the occurrence of invasive Candida albicans infection with disseminated cutaneous Candida granulomas in a patient with aplastic anaemia after viral hepatitis. Fungal elements in a skin biopsy specimen were detected by PAS stain and identified as Candida sp. by immunohistochemistry directed against the C. albicans mannan surface antigen. Based on rapid diagnosis of Candida granuloma and by Candida-positive cultures of blood and swabs, systemic treatment with liposomal amphotericin B led to survival of the patient.

Adult↗
PubMed1996

Graft failure after donor leucocyte infusion in relapsed chronic myeloid leukaemia: successful treatment with cyclophosphamide and antithymocyte globulin followed by peripheral blood stem cell infusion.

We report a patient with chronic myeloid leukaemia who underwent allogeneic marrow transplantation (BMT) but had a molecular relapse 5 months and haematological relapse 15 months after BMT. Since therapy with alpha-interferon had been ineffective he received leucocyte infusions from his sibling donor. He developed acute graft-versus-host disease and became aplastic 6 weeks later. Despite donor marrow infusion and cytokine stimulation marrow aplasia persisted for 13 weeks. Then, donors' peripheral blood stem cells were given after conditioning with cyclophosphamide and antithymocyte globulin resulting in trilineage engraftment of donor haemopoiesis. Since then, the patient has been in continuous molecular remission for 11 months.

Antilymphocyte Serum↗
PubMed1995

Microangiopathy following allogeneic marrow transplantation. Association with cyclosporine and methylprednisolone for graft-versus-host disease prophylaxis.

A microangiopathic syndrome was observed in 3 of 14 (21%) patients receiving cyclosporine and methylprednisolone (CSA-MP) for graft-versus-host disease (GVHD) prophylaxis between January 1991 and June 1992 at our center. The syndrome consisted of neurological abnormalities, arterial hypertension, intravascular hemolysis with red cell fragmentation, and a drop in platelet counts after allogeneic bone marrow transplantation (BMT) for hematological malignancy, and it occurred around day 50 after BMT. Treatment with plasma exchanges against fresh-frozen plasma resulted in a decrease of serum lactate dehydrogenase and an improvement of neurological symptoms. We compared CSA-MP patients retrospectively with patients who had received cyclosporine and methotrexate (CSA-MTX) for GVHD prophylaxis (n = 70) at our institution. All patients in both groups engrafted. Day 100 survival (80% vs. 79%) and transplant-related mortality (16% vs. 14%) were identical in the two groups. CSA-MP patients had significantly more acute GVHD II-IV (57% vs. 17%, P < 0.01). Arterial hypertension (P < 0.01) and neurological symptoms (P < 0.01) were significantly more frequent in the CSA-MP group. The 11 asymptomatic CSA-MP patients had significantly higher lactate dehydrogenase levels (P < 0.01) and lower platelet counts (P < 0.01) at 40, 60, and 100 days after BMT, which suggests the presence of a subclinical form of microangiopathy. Significantly higher plasma levels of von Willebrand factor antigen in CSA-MP patients on day 50 after BMT (P < 0.05) and absence of large von Willebrand factor multimers on gel electrophoresis in 4 of 13 (31%) CSA-MP patients compared with 0 of 14 (0%) CSA-MTX patients (P < 0.01) further suggest profound endothelial damage in patients receiving CSA-MP for GVHD prophylaxis.

Adult↗
PubMed1995

Emergency intubation with the Combitube in two cases of difficult airway management.

The airway was managed successfully in two cases of difficult intubation using the Combitube, a new device for emergency intubation, which combines the functions of an oesophageal obturator airway and a conventional endotracheal airway. One patient could not be intubated due to lockjaw; in the other patient, the vocal cords could not be seen because of continued vomiting. The cases illustrate the benefit of the Combitube during emergency intubation for different problems and its effectiveness as an alternative to traditional intubation techniques.

Aged↗