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Biomedical subjects

M Bargetzi

Publications and source records attributed to M Bargetzi.

17 recordsLinked to original sources
PubMed2006

Combination of broad molecular screening and cytogenetic analysis for genetic risk assignment and diagnosis in patients with acute leukemia.

We evaluated the impact of genetic analysis combining cytogenetics and broad molecular screening on leukemia diagnosis according to World Health Organization (WHO) and on genetic risk assignment. A two-step nested multiplex RT-PCR assay was used that allowed the detection of 29 fusion transcripts. A total of 186 patients (104 males (56%), 174 adults (94%), 12 children (6%), 155 AML (83%), 31 ALL (17%)) characterized by morphology and immunophenotyping were included. Of these 186 patients, 120 (65%) had a genetic abnormality. Molecular typing revealed a fusion transcript in 49 (26%) patients and cytogenetic analysis revealed an abnormal karyotype in 119 (64%). A total of 27 (14%) cases were genetically classified as favorable, 107 (58%) intermediate and 52 (28%) unfavorable. For 38 (20%) patients, there was a discrepancy in the genetic risk assignments obtained from broad molecular screening and cytogenetics. Cryptic fusion transcripts in nine (5%) patients changed the genetic risk assignment in four and the WHO classification in four patients. In 34 patients (18%), cytogenetics defined the risk assignment by revealing structural and numerical chromosomal abnormalities not detected by molecular screening. Broad molecular screening and cytogenetics are complementary in the diagnosis and genetic risk assignment of acute leukemia.

Acute Disease↗
PubMed2005

Change in stem cell source for hematopoietic stem cell transplantation (HSCT) in Europe: a report of the EBMT activity survey 2003.

This EBMT activity survey presents the status of hematopoietic stem cell transplantation (HSCT) in Europe 2003 and focuses on changes in stem cell source over the last decade. There were 21 028 first HSCT, 7091 allogeneic (34%), 13 937 autologous (66%) and 4179 additional re- or multiple transplants reported from 597 centers in 42 European countries in the year 2003. Main indications were leukemias (6613 (31%; 78% allogeneic)); lymphomas (11 571 (55%; 93% autologous)); solid tumors (1792 (9%; 92% autologous)) and nonmalignant disorders (898 (5%; 93% allogeneic)). In 1991, the vast majority of autologous and all allogeneic HSCT were still bone marrow (BM) transplants. Stem cell source changed rapidly to peripheral blood (PB) for autologous HSCT between 1992 and 1996. In 2003, 97% of autologous HSCT were PB derived. The change to PB for allogeneic HSCT followed 3 years later and occurred at a lower rate. In 2003, 65% of all allogeneic HSCT were PB derived. The change in stem cell source was not homogeneous. It was associated with donor type, main diagnosis, disease stage and it differed between European countries. In 2003, bone marrow remains a significant source of stem cells in some European countries for autologous HSCT and for nonmalignant disorders in allogeneic HSCT.

Bone Marrow Transplantation↗
PubMed2005

Polymorphisms of UDP-glucuronosyltransferase 1A7 are not involved in pancreatic diseases.

BACKGROUND: Xenobiotic mediated cellular injury is thought to play a major role in the pathogenesis of pancreatic diseases. Genetic variations that reduce the expression or activity of detoxifying phase II biotransformation enzymes such as the UDP-glucuronosyltransferases might be important in this respect. Recently, a UGT1A7 low detoxification activity allele, UGT1A7*3, has been linked to pancreatic cancer and alcoholic chronic pancreatitis. OBJECTIVE: To investigate whether UGT1A7 polymorphisms contribute to the risk of pancreatitis and pancreatic cancer. METHODS: Genetic polymorphisms in the UGT1A7 gene were assessed in a large cohort of patients with different types of pancreatitis and pancreatic cancer originating from the Czech Republic (n = 93), Germany (n = 638), Netherlands (n = 136), and Switzerland (n = 106), and in healthy (n = 1409) and alcoholic (n = 123) controls from the same populations. Polymorphisms were determined by melting curve analysis using fluorescence resonance energy transfer probes. In addition, 229 Dutch subjects were analysed by restriction fragment length polymorphism. RESULTS: The frequencies of UGT1A7 genotypes did not differ between patients with acute or chronic pancreatitis or pancreatic adenocarcinoma and alcoholic and healthy controls. CONCLUSIONS: The data suggest that, in contrast to earlier studies, UGT1A7 polymorphisms do not predispose patients to the development of pancreatic cancer and pancreatitis.

Adenocarcinoma↗
PubMed2004

'Agglutination and flocculation' of stem cells collected by apheresis due to cryofibrinogen.

Collection of peripheral stem cells by apheresis is a well-described process. Here, investigations concerning 'agglutination and flocculation' of stem cells collected from two patients are described. In both cases, cryoproteins were observed and cryofibrinogen was identified using high-resolution two-dimensional electrophoresis. In one case, peripheral stem cells were collected after a second course of mobilization, and the cells were immediately washed at 37 degrees C before being frozen, allowing their use, despite the presence of cryofibrinogen. In the other case, 'agglutination' was reversed by warming the bag, and plasma was removed before freezing.

Agglutination↗
PubMed2004

Familial cutaneous mycosis fungoides: successful treatment with a combination of gemcitabine and alemtuzumab.

We report a familial cutaneous T-cell lymphoma in father and son. After different treatment modalities without lasting responses, the son was treated with gemcitabine as single agent and due to insufficient effect with alemtuzumab monotherapy. Only after the two drugs had been combined did we observe a remarkable response of the skin lesions and disappearance of enlarged lymph nodes. The combined treatment with gemcitabine and alemtuzumab was well tolerated, and no increased toxicity was noted. The combination of these two active agents may provide an additional option in the treatment of cutaneous T-cell lymphoma.

Adult↗
PubMed2000

Phase II study of docetaxel alternating with cisplatin in chemotherapy-naïve patients with advanced non-small cell lung cancer.

The objective of this study was to evaluate a regimen of full doses of docetaxel and cisplatin, using an alternating schedule, as first-line therapy for patients with inoperable non-small cell lung cancer (NSCLC). The standard concomitant schedule does not allow full doses of both drugs to be administered. We wanted to see if there was an advantage to be gained by administering full doses of both docetaxel and cisplatin, using a different schedule. Docetaxel 100 mg/m2 was given once every 6 weeks from week 1 and cisplatin (120 mg/m2 for two doses and 100 mg/m2 thereafter) once every 6 weeks from week 4, for six cycles (three docetaxel and three cisplatin). Thirty-six of the 44 patients enrolled were evaluable for efficacy. Forty-eight percent of the patients had good (KPS 90-100%) performance status. A median of five cycles was administered, for which no dose reductions were necessary. There were 13 of 36 partial responses (36%; 95% CI 21-54%) and 15 of 36 patients achieved stable disease (42%). The median duration of response was 10.5 months, the median time to progression was 4.5 months and the median survival was 9 months. The 1 and 2 year survival rates were 39 and 16%, respectively. The most frequent grade 3-4 toxicities were nausea (23% of patients), vomiting (18%) and neutropenia (77%). Infections were also common, but not severe. The alternating schedule produced response, toxicity and survival figures that compared favorable with those using the concomitant schedule. This study could serve as a model for future studies of non-cisplatin-containing regimens, in which full doses of docetaxel could alternate with full doses of other new agents active against NSCLC.

Adult↗
PubMed1999

[Burkitt's lymphoma--a case report].

Burkitt-lymphoma is a rare disease, that belongs to the aggressive Non-Hodgkin-lymphomas. Next to histology, that shows a characteristic pattern, and immunophenotyping additional cytogenetic and molecular biology techniques are used to demonstrate in most cases a translocation of the oncogen c-myc on chromosome 8 to any of the immunoglobulin genes on chromosome 14, 2 or 22. With short term intensive chemotherapies a cure rate of 85-95% of patients with Burkitt-lymphoma can be obtained today.

Adult↗
PubMed1998

Repeated treatment with horse antilymphocyte globulin for severe aplastic anaemia.

In a single-centre study the feasibility and efficacy of repeated antilymphocyte globulin (ALG) for patients with severe aplastic anaemia (SAA) not responding to an initial ALG treatment or relapsing after initial response to ALG was evaluated. 139 consecutive patients with newly diagnosed SAA were treated with ALG between 1976 and 1995. 89 patients responded to a first course; 50 patients did not become transfusion independent. Of the 89 responders, 66 remained in remission, 23 relapsed. 43 patients received a second or subsequent course of ALG for failure to respond (n = 25) or relapse (n = 18) and were given a total of 53 courses. Acute reactions in the multiply exposed patients occurred during the first ALG treatment in 11 (26%) and during subsequent exposures in 16/53 courses (30%; P > 0.2). Incidence of serum sickness was 63% (27/43) after the initial course compared to 57% (30/53) after subsequent courses (P > 0.2), but clinical signs of serum sickness occurred earlier after repeated (median 6 d) as compared to initial exposure (13d; P = 0.008). Transfusion-independent haemopoiesis was achieved in 27/43 (63%) and survival probabilities for the 43 patients receiving multiple courses of ALG was 52 +/- 8% at 10 years. The probability of developing a late clonal disorder was 53 +/- 10% after multiple, as compared to 34 +/- 7% after single exposure (P = 0.15). No difference in results was observed between patients retreated for failure to first ALG or for relapse. ALG of the same species can be repeated without increased risks of side-effects in patients with SAA. A second or subsequent course of ALG from the same source can be effective when the first course has failed.

Adolescent↗
PubMed1996

[Transplantation of allogeneic peripheral hematopoietic progenitor cells instead of bone marrow].

In a pilot study we tested the feasibility and safety of peripheral blood precursor cells instead of bone marrow cells for allogeneic transplantation. 13 patients, 7 male and 6 female between 24 and 52 years of age with hematological malignancies (10 with acute leukemias, 3 with myeloproliferative syndromes-were conditioned for bone marrow transplantation with VP-16, cyclophosphamide and total body irradiation followed by graft-versus-host disease prophylaxis with cyclosporin and methotrexate. Precursor cells were mobilized in the donors by granulocyte colony stimulating factor (G-CSF, Neupogen) 10 micrograms/kg s.c. from day-5 on. A total of 14.05 x 10(8) nucleated cells/kg recipient body weight (range 9.52-20.23 x 10(8)/kg), corresponding 6.82 x 10(6)/kg CD 34+ cells (range 1.43-15.84 x 10(8)/kg) or 113.9 x 10(4) CFU/kg (range 45.15-431.64 x 10(4)/kg) were collected by 3 phereses (1 patient 5 phereses) of 27-45 liters and infused without further manipulation. All patients engrafted with a recovery of total white blood cell count > 1 x 10(9)/l on day 15 (day 10-26) and of platelets > 20 x 10(9)/l on day +18 (day 12-39). 11 of the 12 patients developed aGvHD, 8 with grade II, 3 with grade > or = II. 9 of 13 patients are alive and well +4 to +16 months posttransplant, 3 patients died of aGvHD, one of veno-occlusive disease. These preliminary results confirm the capacity of peripheral blood precursor cells for rapid and complete engraftment in the allogeneic setting. Whether they induce more or equal aGvHD is an open question. Their value in allogeneic transplantation is currently under investigation in prospective randomized trials.

Adult↗
PubMed1996

[Autologous transplantation of hematopoietic precursor cells following CD34 selection].

Peripheral blood is increasingly used instead of bone marrow as a source of hemopoietic precursor cells for transplantation. The optimal technique still needs to be defined. Selection of CD34+ cells in transplant material may be of benefit in allogeneic and autologous peripheral blood precursor cell transplantation (PBPCT), since it allows elimination of unwanted CD34-negative cells, such as T-cells and contaminating tumor cells. We have evaluated the feasibility of CD34 selection in PB transplants and studied hemopoietic reconstitution after autologous transplantation of CD34 selected precursor cells. Between August 1994 and June 1995 CD34 selection was performed on 12 transplants for 9 patients with malignant disease (non-Hodgkin lymphoma [n = 5]; Ewing sarcoma [n = 1]; chronic lymphocytic leukemia [n = 1]; breast cancer [n = 1]; multiple myeloma [n = 1]). PBPC were collected with a Fenwall CS 3000 harvester after stimulation with G-CSF. For selection of CD34+ cells the Ceprate LC34 system (CellPro) was used. A median CD34 purity of 73% (range 40-94%) was achieved. The median number of CD34 positive cells per transplant was 4.8 x 10(6)/kg body weight (range 0.7-15.8). The median number of colony forming cells per transplant was 31 x 10(4)/kg body weight (range 1.5-131.3). For autologous PBPCT the minimal number of CD34 positive cells required in the transplantate was arbitrarily set at 1.0 x 10(6)/kg body weight. This number was achieved in 10 of the 12 transplants. The median loss of CD34+ cells during selection was 1.5 x 10(6)/kg body weight (range 0.2-6.4). In 2 patients the total number was reduced to below the critical value of 1.0 x 10(6)/kg. 7 of the 9 patients received the CD34 selected transplant after intensive chemotherapy and irradiation. The median follow-up time after PBPCT was 196 days (range 62-278). All 7 patients are now alive and with normal hemopoietic function. A granulocyte count above 0.5 x 10(9)/l and a platelet count above 20 x 10(9)/l was achieved on day 14 (median), and on day 19 after PBPCT. We conclude that CD34 selection is technically feasible and that CD34 selected cells can be used for PBPCT. The procedure is time consuming and expensive; it requires complex organization at laboratory level, and the benefit of CD34 selection with regard to T-cell depletion and tumor purging still needs to be proven. However, CD34+ selection is likely to open new perspectives in transplantation medicine.

Adolescent↗
PubMed1996

Splenectomy as an adjuvant measure in the treatment of severe aplastic anaemia.

The role of splenectomy in aplastic anaemia (AA) is controversial. The hazards of operating on a severely pancytopenic patient, the fear of compromising the patient's immune function, and the improvement of non-surgical treatment have made splenectomy unpopular in this disease. We have evaluated positive and adverse effects of splenectomy in 80 patients with severe aplastic anaemia (SAA) treated with antilymphocyte globulin (ALG) (group A), using 52 nonsplenectomized ALG patients as controls (group B). All patients survived the operation. Nonfatal complications of surgery occurred in 10 (12.5%). Splenectomy induced a significant increase of peripheral blood neutrophils, reticulocytes and platelets within 2 weeks, followed by a continuous increase of all values over the following weeks. 28/132 patients (21%) developed a late clonal disorder of haemopoiesis, paroxysmal nocturnal haemoglobinuria (PNH) or myelodysplastic syndrome (MDS), or both. Their incidence was identical in groups A and B. 13/28 (59%) died, 10/17 (59%) in group A and 3/11 (27%) in group B (not significant (n.s.)). Overall probability of survival at 18 years after ALG was 51+/-6% for group A and 61+/-7% for group B (n.s.). We conclude that splenectomy in AA is safe. It induces an immediate increase of peripheral blood counts and, thereafter, a continuous improvement of haemopoiesis. It does not increase the incidence of late clonal complications but has a borderline effect on mortality from these disorders. Splenectomy should be reconsidered in selective nontransplanted patients who have prolonged transfusion requirements despite otherwise optimal treatment.

Adolescent↗
PubMed1995

[Flow cytometry identification of CD34-positive cells].

In the present study three clinical applications of flow-cytometric quantification of CD34-positive cells in the field of blood and marrow transplantation are evaluated. By daily determination of CD34-positive cells in the peripheral blood after mobilization of stem cells with chemotherapy or growth-factors it is possible to set the optimal time for collection of the transplant material. Thereafter the yield of CD34-positive cells within the harvested material is determined. Finally, the efficacy of positive CD34 selection using a biotin-avidin column is evaluated. Initial experience is presented here.

Antigens, CD↗
PubMed1995

[Late idiopathic pneumopathy following bone marrow transplantation].

4 of the 198 patients treated by bone marrow transplantation in Basel, Switzerland, with a follow-up of more than one year after therapy, developed a severe restrictive pneumopathy. In none of the 4 patients could an infectious pathogen be isolated, but all of them had signs of a chronic graft-versus-host disease. The 4 cases are described in detail.

Adolescent↗
PubMed1994

Relationship between soluble tumor necrosis factor (TNF) receptors and TNF alpha during immunotherapy with interleukin-2 and/or interferon alpha.

Eleven metastatic cancer patients were studied during three different regimens of immunotherapy with interleukin-2 (IL-2) and/or interferon alpha (IFN alpha): group A received 4 days of IL-2 i.a. infusion (n = 3), group B IFN alpha s.c. during 5 days (n = 4), followed on day 3 by 5 days of a continuous IL-2 i.v. infusion, and group C had 4 days of IL-2 i.v. infusion together with s.c. IFN alpha on days 1 and 4 (n = 4). Soluble tumor necrosis factor receptors (sTNFR) p55 and p75 and TNF alpha concentrations in serum were analyzed before therapy and daily during 8 days of the first therapy cycle. sTNFR was measured by radioimmunoassay. sTNFR p55 increased in all patient groups from a baseline value of 5.2 +/- 0.9 ng/ml to a maximum of 13.6 +/- 1.2 ng/ml by days 3-4 (P = 0.003). sTNFR p75 increased from 7.6 +/- 1.1 ng/ml to peak values of 30.1 +/- 2.6 ng/ml in groups A and B (P = 0.02). In group C the sTNFR p75 response was weak (NS). In group B, the increase of both p55 and p75 occurred only after addition of IL-2 to IFN alpha. TNF alpha increased weakly during treatment with IFN alpha alone (group B); it rose strongly during IL-2 and the combined treatment (groups A-C) from 8 +/- 2 pg/ml to 115 +/- 13 pg/ml (P = 0.003). In group B, it reached the maximum 24 h after addition of IL-2 to IFN alpha and decreased thereafter. There was a significant relationship between TNF alpha and sTNFR p55 or sTNFR p75 in groups A and C, (P = 0.001), but not in group B. Group C was also investigated during the third therapy cycle. The increase of sTNFR p75 was stronger (P = 0.01) and that of TNF alpha weaker than in the first cycle; the sTNFR p55 response was similar in both cycles. In conclusion sTNFR p55 and p75 are rapidly induced during IL-2 and IL-2+ IFN alpha treatment, the increase of sTNF receptors parallels or exceeds that of TNF alpha and may influence the immunomodulatory effects of TNF alpha during cytokine therapy.

Adult↗
PubMed1991

Quantitation of intrinsic drug-metabolizing capacity in human liver biopsy specimens: support for the intact-hepatocyte theory.

Hepatic drug metabolism is decreased in patients with severe liver disease, but it is unclear to what extent this is due to altered hepatic blood flow or reduced intrinsic metabolic capacity. In this study we quantitated in needle-biopsy specimens the intrinsic capacity of liver tissue from 67 patients with mild liver disease (n = 36), chronic active hepatitis (n = 16) and cirrhosis (n = 15) to metabolize two model compounds in vitro. Hydroxylation of the low-extraction drug bufuralol resulted in the formation of 251 +/- 25 nmol 1'OH-bufuralol/gm wet wt/hr in mildly diseased liver tissue and was significantly (p less than 0.01) reduced in liver tissue exhibiting chronic active hepatitis (166 +/- 23 nmol/gm wet wt/hr) and cirrhosis (124 +/- 21 nmol/gm wet wt/hr). The formation rates of monoethylglycinexylidide, the main metabolite of the high-extraction drug lidocaine, varied widely and were not significantly different among the three groups. To relate the drug-metabolizing capacity to the hepatocyte content of liver tissue, morphometrical study was performed in the biopsy pieces originally submitted. The metabolic activity of each biopsy piece was then related to the fractional volume of hepatocytes it was calculated to contain. In mildly diseased liver tissue 355 +/- 35 nmol 1'OH-bufuralol/ml hepatocytes x hr or 12.4 +/- 1.0 mumol monoethylglycinexylidide/ml hepatocytes x hr- and in cirrhotic liver tissue 306 +/- 49 nmol 1'OH-bufuralol/ml hepatocytes x hr or 15.3 +/- 3.0 mumol monoethylglycinexylidide/ml hepatocytes x hr--were formed, respectively, and these differences were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1990

[Pharmacogenetics for the practicing physician].

An important source of interindividual differences in drug action are inherited differences in the pharmacokinetics and pharmacodynamics of many drugs. Besides some well-known but rarely occurring examples of unusual drug action, the inherited variations of drug metabolism are of particular clinical importance, as a relationship between the defect of metabolism and the effects and toxicity of the drugs involved has been observed. Recent investigations were able to elucidate many of the molecular mechanisms responsible for these genetic defects.

Humans↗