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Biomedical subjects

A Ganser

Publications and source records attributed to A Ganser.

At least 289 records · Page 16Linked to original sources
PubMed1983

Cytogenetic studies in chronic myeloproliferative disorders.

Cytogenetic studies were performed on 113 patients with the clinical diagnosis of a chronic myeloproliferative disorder: 70 were classified as chronic myelocytic leukemia (CML), 8 as polycythemia vera (PV), 10 as osteomyelofibrosis/sclerosis (OMS), and 15 as unclassified myeloproliferative disorder (UMPD). 2 patients, 1 with UMPD and 1 with subacute leukemia, were reclassified as CML after the cytogenetic study. In the group comprising PV, OMS, and UMPD, 28% (9/32) had a chromosomally abnormal clone. The chromosomes affected involved those reported to show nonrandom alterations in myeloproliferative disorders, namely the chromosomes, 1, 7, 8, and 9.4 patients exhibited a loss of the Y-chromosome.

Adult↗
PubMed1983

The fate of cells with chromosome aberrations after total-body irradiation and bone marrow transplantation.

Cytogenetic studies were done on bone marrow cells and peripheral lymphocytes of four patients (three with acute nonlymphocytic leukemia, one with aplastic anemia) at various intervals up to 861 days after total-body X irradiation (TBI) at doses between 4.5 and 10 Gy (450-1000 rad) followed by syngeneic or allogeneic bone marrow transplantation. Whereas no radiation-induced aberrations could be found in the bone marrow, apart from a transient finding in the patient with the lowest radiation dose, aberrant metaphases were seen in the peripheral lymphocytes of three patients in the range from 2.5 to 46% even at 861 days after the exposure. There were no demonstrable aberrations related to TBI in the only patient developing graft-versus-host disease. The dicentric yield as determined in the aberrant metaphases with 46 centromeres ranged between 3.4 +/- 1.3 and 4.9 +/- 0.4. In one patient it was demonstrated by BUdR-labeling that after 10 Gy (1000 rad) TBI the surviving and heavily damaged lymphocytes can go into cell cycle and reach at least the third mitosis. The percentage of aberrant cells diminished by about 25% at each mitotic division.

Acute Disease↗
PubMed1982

Cytogenetic studies using HPCM-stimulated short-term liquid cultures of circulating hemopoietic precursor cells in patients with myelofibrosis.

Cytogenetic studies were performed on nine patients with myelofibrosis. Mononuclear cells from the peripheral blood were cultured for two days in the presence of human placenta-conditioned medium (HPCM) prior to the preparation of metaphases. Two patients showed abnormal clones. In one of them the Y chromosome was missing. In the other patient the abnormal clone was characterized by the involvement of the chromosomes 7 and 9 (46,XX,7q-,-9,+mar). The significance of cytogenetically abnormal circulating hemopoietic precursor cells in patients with myelofibrosis is discussed.

Adult↗
PubMed1975

Unique enzymes of purified microsomes from pig fundic mucosa. K+-stimulated adenosine triphosphatase and K+-stimulated pNPPase.

Microsomal fractions from homogenates of pig gastric fundic mucosa showed high levels of K+-stimulated adenosine triphosphatase (ATPase) and K+-stimulated phosphatase. Similar preparations from antral mucosa showed virtually no such activity. Because of mitochondrial contamination the fundic microsomes were further separated by sucrose density gradient centrifugation. A low density band of membranes (peak 1.12 to 1.13 g per ml) possessed all of the K+-stimulated enzyme activities. Morphological features and the abundant glycoproteins of the low density microsomes suggested they might be derived from the tubulovesicles of oxyntic cells. Mitochondrial and ribosomal markers were associated with membranes with much higher densities (greater than 1.22). The K+-stimulated ATPase has a pH optimum of 7.5 and required Mg++, but neither Na+ nor ouabain had any appreciable effect on the activity. Stimulation of basal ATPase by K+ ranged from 1.5 to 3.0-fold with an apparent Ka for activation between 0.2 to 0.4 mM K+. Addition of various K+ ionophoretic substances (e.g., gramicidin) produced further stimulation of K+-ATPase up to 6 times the basal rate. The mean activities for seven separate preparations of purified low density pig fundic microsomes were as follows (micromoles of ATP hydrolyzed per mg protein per hr +/- SEM); basal ATPase, 15.8 +/- 2.8; plus 10 mM K+, 29.3 +/- 4.5; plus 10 mM K+ and 10(-5) M gramicidin, 45.2 +/- 5.2. Neither the basal ATPase nor the K+-stimulated rates were altered by HCO3- or Cl-. The occurrence of these active and unique enzyme activities in the oxyntic region of gastric mucosa suggest some relation with secretory activity. Possible functional roles are discussed.

4-Nitrophenylphosphatase↗
PubMedDate not supplied

Outcome of peripheral blood stem cell mobilization in advanced phases of CML is dependent on the type of chemotherapy applied.

High-dose chemotherapy with autologous transplantation of in vivo purged PBSC is a novel investigational approach to treating chronic myelogenous leukemia (CML) patients not responsive to conventional therapy with interferon-alpha (IFN-alpha) and not eligible for allogeneic transplantation. PBSC mobilization using either '5+2/7+3'-type chemotherapy or 'mini-ICE/ ICE' chemotherapy was investigated in 43 patients with advanced phases of Philadelphia (Ph)-positive CML. Thirty patients were in late chronic phase (>12 months post diagnosis) and 13 patients in accelerated phase (AP) or blast crisis (BC). Contamination with Ph-positive cells was evaluated in harvests from 37/43 patients. The outcome of PBSC mobilization was dependent on the type of chemotherapy administered: a complete or major cytogenetic response (<35% Ph-positive metaphases) in leukapheresis collections was obtained in ten of 15 patients treated with 'mini-ICE/ICE' but in only three of 28 patients treated with '5 + 2/7 + 3' chemotherapy. One patient (1/43) in blast crisis died during mobilization therapy (2%). Twenty-five patients underwent PBSC transplantation and all of them engrafted successfully. Transplantation-related mortality was 0%. The data show that in advanced phases of CML the chance of harvesting Ph-negative peripheral blood stem cells depends on the type of chemotherapy used for mobilization.

Adult↗
PubMedDate not supplied

Early detection of chronic disseminated Candida infection in leukemia patients with febrile neutropenia: value of computer-assisted serial ultrasound documentation.

Computer tomography (CT) is known to be as sensitive as magnetic resonance imaging (MRI) in detecting fungal microabscesses in chronic disseminated candidiasis. However, all imaging techniques have to be repeated in cases of suspected fungal infection. Therefore, use of the CT or MRI scan is limited. Only ultrasound (US) examinations can be repeated as often as needed. The disadvantage of US is a lack of sufficient documentation. We analyzed the value of computer-assisted documentation in serial ultrasonography of leukemia patients with suspected chronic disseminated candidiasis. From November 1996 until October 1997, a total of 220 ultrasound examinations (Kranzbühler Logiq 500, 3.5 MHz convex array) were performed in 58 patients undergoing intensive chemotherapy. Initial US pictures were stored on a personal computer and compared with the live US at the time of reevaluation in cases of persistent fever. Ultrasound detected microabscesses in liver and/or spleen in eight of the 58 patients. Diagnosis was confirmed by autopsy/biopsy (n = 6), blood culture (n = 1), and a significant Candida antibody titer (n = 1). Focal lesions occurred only after neutrophil recovery. However, a newly evolving nonhomogeneous, micronodular pattern of liver and spleen occurred during febrile neutropenia in three patients, and two of these developed focal lesions subsequently. Follow-up was easy, since US pictures could be compared directly with stored examinations on screen. We conclude that serial US is sensitive in detecting microabscesses in the liver or the spleen. Computer-assisted US documentation proved to be a helpful tool for detection as well as in the follow-up of patients with chronic disseminated candidiasis.

Adolescent↗
PubMedDate not supplied

Changes in the haematopoietic progenitor cell compartment in the acquired immunodeficiency syndrome.

In order to elucidate the mechanisms responsible for the disturbances of haematopoiesis in HIV-infected individuals, bone marrow from 25 patients with either ARC or AIDS was studied. There is a stage-related decrease in CFU-GEMM, CFU-MK, BFU-E and CFU-GM, with the latter being least affected. This decrease is inversely correlated with the number of circulating CD4 cells and the CD4/CD8 ratio. Immunohistochemical and in situ hybridization studies of haematopoietic colonies failed to demonstrate HIV infection of haematopoietic cells. Neither the depletion of adherent mononuclear cells from haematopoietic cell cultures nor the addition of plasma containing antibodies against HIV gp120 could demonstrate an inhibitory effect of HIV-infected macrophages or immune-mediated progenitor cell lysis, respectively. Hence, imbalances of T-cell subpopulations appear to be mainly responsible for the progressive impairment of proliferation and differentiation of bone marrow progenitor cells observed in HIV-infected individuals.

AIDS-Related Complex↗
PubMedDate not supplied

Infection of granulocyte/monocyte progenitor cells with HIV1.

In order to study whether cytopathic HIV1 infection of haemopoietic progenitor cells is involved in the derangement of haemopoiesis in patients with HIV1 infection, we infected enriched progenitor cells with HIV1, by addition of viral inoculate supernatants from HIV1-infected peripheral blood mononuclear cells or by coculture with HIV1-infected monocytes/macrophages. Progenitor cells were seeded into colony assays and single colonies were chosen for HIV1 mRNA determination by in situ hybridization. Growth of progenitors was not affected by infection. However, up to 42% of colonies of pluripotent progenitor cells (colony-forming unit/granulocyte-erythrocyte-monocyte; CFU-GEM) and committed progenitor cells CFU/granulocyte-monocyte (CFM-GM) contained HIV1 mRNA-expressing cells. In addition, we studied HIV1 infection of progenitor cells from the bone marrow of 6 patients with AIDS or AIDS-related complex. Two patients were negative, two had a few colonies expressing HIV1 mRNA in a minority of cells, and in the remaining two, up to 11% of CFU-GM contained HIV1-expressing cells. Thus, infection of progenitor cells with HIV1 was achieved experimentally in vitro and occurs in vivo. However, growth of progenitors after in vitro infection continues and therefore HIV1 infection does not seem to contribute directly to the reduced incidence of haemopoietic progenitor cells in vivo.

Granulocytes↗
PubMedDate not supplied

Decreased haematopoietic colony growth in long-term bone marrow cultures of HIV-positive patients.

Deficiencies in bone marrow stromal cells, i.e. fibroblasts, macrophages, endothelial cells and adipocytes, are considered to play a pathophysiological role in HIV-associated haematopoietic failure. Long-term bone marrow cultures (LTBMC) enable the longitudinal investigation of haematopoietic progenitor cell and bone marrow stromal growth. Therefore, in this study, the haematopoietic colony growth of bone marrow from patients with severe HIV infection was compared to that from healthy controls in LTBMC. The total cumulated number of colony-forming units/granulocyte-macrophage (CFU-GM) was 6.7-fold higher (293.6% vs. 44.0%, p < 0.01), that of colony-forming units/granulocyte-erythrocyte-macrophage-megakaryocyte (CFU-GEMM) was 3.5-fold higher (28.7% vs 8.3%), and that of burst-forming units/erythrocyte (BFU-E) was 31.1-fold higher (68.4% vs 2.2%) than that from HIV-positive patients, respectively (colony number before LTBMC = 100%). In contrast, the cumulated cell number at the end of LTBMC from HIV-positive patients was not reduced (cell numbers in percent of initially seeded cells: HIV-positive 418.4%, HIV-negative 397.1%). The significantly reduced colony-forming capacity over a significantly shorter time span, without reduction in the absolute cell number, in LTBMC from patients with severe HIV-infection as compared to healthy controls, suggests that uncoupling between cell proliferation and differentiation is a pathophysiological mechanism in HIV-dependent haematopoietic failure.

Adult↗
PubMedDate not supplied

New strategies in the treatment of infectious complications in haematology and oncology: is there a role for out-patient antibiotic treatment of febrile neutropenia?

Febrile neutropenia is associated with a significant risk of complications and mortality. Patients with neutropenia secondary to cytostatic chemotherapy who develop fever are normally admitted to hospital and treated promptly with broad-spectrum antibiotics. Over the last 10 years, chemotherapy for solid tumours has been shifting out of the hospital setting into the ambit of community-based oncologists, and out-patient treatment with complex multidrug protocols is becoming increasingly common. In North America high-dose protocols combined with peripheral blood stem cell transfusion are already being administered on an out-patient basis. With the increase in the numbers of out-patients undergoing multidrug chemotherapy, there has been a corresponding rise in the severity and duration of neutropenia and in the incidence of associated infections. Patients with neutropenia of short duration (<7 days) and fever are at a relatively low risk for complications, and in these circumstances, out-patient antibiotic treatment is an alternative to costly hospitalisation. Drugs, whose antimicrobial coverage and pharmacokinetics make them particularly suitable for out-patient treatment of febrile neutropenia, include intravenous and oral quinolones and, for once-daily dosing, intravenous glycopeptides, ceftriaxone and intravenous aminoglycosides. Response rates of 60-95% have been achieved with such regimens in clinical trials, with hospital admission avoided in 75-95% of the cases. There is no doubt that out-patient treatment improves the quality of life of cancer patients. In Europe, however, there is a need for randomised clinical trials to support the establishment of out-patient-based treatment of febrile neutropenia. Out-patient antibiotic treatment of febrile neutropenia is still not standard practice, and community-based providers of such treatment must be adequately equipped and experienced in the management of this condition.

Anti-Bacterial Agents↗
PubMedDate not supplied

Intensive intravenous amphotericin B for prophylaxis of systemic fungal infections. Results of a prospective controlled pilot study in acute leukemia patients.

BACKGROUND: Invasive fungal infections are an increasing cause of morbidity in acute leukemia (AL) patients. METHODS: In a prospective pilot trial, the safety and efficacy of antifungal prophylaxis with intravenous (i.v.) amphotericin B (AMB; 1 mg/kg every 48 h) was studied in 46 consecutive cycles. Prophylaxis with i.v. AMB was carried out in patients treated with intensive chemotherapy for AL and compared with a control of 49 cycles without prophylaxis. RESULTS: Pulmonary infiltrates (5 vs. 23; p < 0.001) and fungal microabscesses in the liver or spleen (0 vs. 6; p = 0.014) occurred significantly less frequently in the prophylaxis group. While there were 3 deaths related to systemic fungal infections in the control group, there were none in the prophylaxis group. Escalation to conventional AMB (1.0 mg/kg/day) was significantly less frequent in the prophylaxis group (9 out of 46 cycles) compared with the control arm (29 out of 49 cycles; p = 0.001). A total of 695 mg of AMB per cycle was administered in the prophylaxis arm, compared with 634 mg/cycle for empirical treatment in the control group (p = 0.6). Infusion-related toxicity was documented in 29% of the cycles of prophylaxis compared with 55% of the cycles of empirical treatment with i.v. AMB in the control group. The nephrotoxicity of AMB prophylaxis was moderate, with >/= WHO degree II reported in 1 out of 46 cycles only. CONCLUSION: Intensive i.v. AMB prophylaxis reduced invasive fungal infections and led to a reduction in fungal microabscesses in the liver or spleen, as well as pulmonary infiltrates, in patients treated for AL. The need for escalation to empirical i.v. AMB treatment was significantly reduced. Intensive AMB prophylaxis was feasible, with moderate adverse effects.

Adult↗
PubMedDate not supplied

Efficacy of a benzalkonium chloride-impregnated central venous catheter to prevent catheter-associated infection in cancer patients.

BACKGROUND: This study was performed to determine the efficacy of a benzalkonium chloride-impregnated central venous catheter (CVC) in preventing catheter-related infection in patients suffering from malignant diseases and undergoing chemotherapy. METHODS: A randomized, prospective clinical trial was carried out to compare the incidence of catheter-related colonization and catheter-related bacteremia using an antiseptic-impregnated CVC (n = 25) with that using a standard triple-lumen CVC (n = 25). RESULTS: All patients were treated with intensive chemotherapy for acute leukemia (n = 28), lymphoma (n = 17) or solid tumors (n = 5). Both study groups presented with similar data in regards to age, insertion site, duration of catheterization and neutropenia period during catheterization, demonstrating a comparable risk for catheter-related colonization. Suspicion of infection led to explantation in 14 versus 15 cases. Catheter-related colonization was proven in 4 cases (16%) and catheter-related bacteremia was observed only once (4%) in both groups. Statistical testing showed no significant differences between the study and control group. CONCLUSIONS: The rate of catheter-related colonization was lower than suspected in this high-risk patient group. The use of benzalkonium chloride-impregnated CVC failed to decrease the incidence of catheter-related colonization and bacteremia in patients with a high risk of infectious complications.

Adult↗
PubMedDate not supplied

Platelet endothelial cell adhesion molecule-1 (PECAM-1): a potential prognostic marker involved in leukocyte infiltration of renal cell carcinoma.

We investigated immunohistochemically the leukocyte infiltrate [CD3, CD4, CD8, CD11a, CD11b, CD14, CD56, VLA-4 and platelet endothelial cell adhesion molecule-1 (PECAM-1)] and the endothelial expression of cell adhesion molecules (PECAM-1, VCAM-1, ICAM-1 and ICAM-2) in 23 renal cell carcinoma tumor tissues. Tumors with a moderate or high density of PECAM-1 positive endothelia showed a stronger infiltration with PECAM-1-positive leukocytes as compared to tumors with a low density of positive endothelia (p<0.0085). Additionally, overall survival of patients who presented with tumors exhibiting a moderate or high density of PECAM-1 endothelia alone or in combination with a PECAM-1-positive infiltrate was extended (median survival: 23.5 months) as compared to patients without these tumor characteristics (median survival: 6.5 months). These results suggest an involvement of PECAM-1 in the process of leukocyte migration and a potential role as a prognostic marker in renal cell carcinoma.

Adult↗
PubMedDate not supplied

Altered expression of beta 1 integrins in renal carcinoma cell lines exposed to vinblastine.

BACKGROUND: Cellular expression of P-glycoprotein (P-gp) which mediates a well characterized mechanism of multidrug resistance (MDR) has been reported previously to be associated with an enhanced tumor dissemination. Since adhesion receptors of the beta 1 integrin family play a substantial role in tumor spread, we studied expression of VLA-1 to -6 in a total of four renal carcinoma cell (RCC) lines prior to and after induction of MDR via exposure to vinblastine. MATERIAL AND METHODS: Surface expression of P-gp and VLA-1 to -6 was determined immunocytochemically in untreated pre-established renal carcinoma cell lines (Caki-1, Caki-2, A498) and a cell line derived from a RCC patient who had received a vinblastine-containing therapy regimen prior to the resection of a local relapse of the tumor (EH). Resistant sublines were cultivated in the presence of 1 ng/ml and 10 ng/ml of vinblastine sulfate, respectively. RESULTS: In all cell lines examined, an increased number of P-gp expressing cells was observed upon exposure to vinblastine. Significant changes of beta 1 integrin expression were observed in three of four RCC cell lines. A de novo expression of VLA-1, VLA-2, and VLA-4 as detected by immunocytochemistry occurred in resistant Caki-1 cells. A498 cells showed an increasing number of VLA-2 positive cells in drug resistant sublines. In contrast, a decrease of VLA-2 and VLA-5 expression was found in EH cells, the only cell line exhibiting P-gp expression prior to vinblastine exposure. Caki-2 cells showed no significant changes of surface integrin expression upon treatment with vinblastine. CONCLUSIONS: Our results demonstrate that induction of drug resistance can be associated with substantial changes of the integrin phenotype in renal carcinoma cell lines. In our experiments, among all VLAs studied, VLA-2 was most frequently altered in expression by RCC cell lines. The significance of these observations for aberrant metastatic properties of multidrug resistant tumor cells will be the subject of further studies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

In vivo administration of recombinant human interleukin-3 elicits an acute phase response involving endogenous synthesis of interleukin-6.

Interleukin-6 has been shown to stimulate in vitro synthesis of C-reactive protein (CCRP) in hepatocytes by enhancing the transcriptional rate of the CRP gene. It has also been demonstrated that IL-6 spurs the terminal differentiation of B-cells into immunoglobulin secreting cells when synergizing with IL-3. IL-6 may therefore act as a prime molecule in the acute phase and immune response. We have administered rh IL-3 to cancer patients in a phase I/II clinical trial. Endogenous IL-6 levels increased in a dose-dependent fashion upon i.v. bolus injection of rh IL-3 and continued to be significantly elevated above pretreatment levels when IL-3 was further administered by the s.c. route. Increases of IL-6 levels were associated with enhanced production of CRP in vivo detected after 24 h of injection. At day 14 of rh IL-3 treatment plasma immunoglobulin concentrations were measured and IgM was found to be increased by greater than 2.5 fold above starting levels. These results indicate that rh IL-3 also augments the acute phase response in vivo and contributes to increased synthesis of IgM and that induction of endogenous IL-6 is involved in these events.

Acute-Phase Proteins↗