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K Possinger

Publications and source records attributed to K Possinger.

At least 37 records · Page 2Linked to original sources
PubMed2001

Tolerability of the cytoprotective agent amifostine in elderly patients receiving chemotherapy: a comparative study.

In order to determine if age and comorbidity influence the tolerability of the cytoprotective agent amifostine, we compared side effects related to amifostine in patients > or = 70 years (group I) with patients < 70 years (group II). We evaluated 268 consecutive administrations of amifostine (119 in group I and 149 in group II, respectively), given i.v. at a dose of 740 mg/m(2) just before platinum-, taxol- or cyclophosphamide-based chemotherapy. Transient hypotension was the most common side effect occurring in association with amifostine. Decreases in systolic blood pressure > 20 mmHg were of similar frequency in both groups (27.1 versus 28.8% of amifostine infusions in group I and II, respectively). Hypotension did not result in medical sequelae in any of the patients. The amifostine infusion was interrupted 16 times in group I and 8 times in group II, respectively, mainly due to hypotension, but could be restarted after a few minutes in all patients except for three cases in group I. Patients in group II more often suffered from nausea/vomiting than in group II (20.8 versus 10.0% in group I). Other subjective symptoms (e.g. warmed, flushed sensation, sneezing, metallic taste, mouth dryness, dizziness and sleepiness) and hypocalcemia occurred with a similar frequency in both groups. Adverse effects associated with amifostine were not observed more frequently in elderly patients than in younger ones, although more elderly patients had a comorbidity than the younger ones.

Adult↗
PubMed2001

Detection of amplifiable messenger RNA in the serum of patients with lung cancer.

Recently, in addition to the detection of circulating tumor cells in peripheral blood of patients with solid tumors, the presence of free circulating nucleic acids in the plasma and serum has also been described. We have focused on the possibility of isolating and amplifying intact extracellular, tumor-related mRNA from the plasma/serum of patients with lung cancer. For this purpose, we established several RT-PCR-based amplification systems for the detection of a panel of five different genes. The expression of these genes was either shown to be restricted to lung tissue or associated with malignancy. We examined two small groups of 18 patients with lung cancer before and during chemotherapy, respectively. The message for beta-actin (control for integrity of the RNA) was detected in all of the analyzed sera from the control group and patients with lung cancer. Analysis of CK-19 expression was positive in the majority of tumor patients, but positive results were also shown in all of the control sera. The expression of MAGE-2 and TTF-1 genes was not observed in any of the patients in either the lymphocyte preparations or serum samples. Expression of the PGP 9.5 gene was observed in the cells of all 18 patients, but mRNA in the serum was only detectable in one case. The hnRNP-B1 mRNA was detectable in 14/18 sera, and Her2/neu-specific mRNA could be amplified from the serum of 7/18 patients. Combining the last two markers, we were able to detect all patients with a malignant lung tumor.

Actins↗
PubMed2001

Differentiation of monoclonal gammopathy of undetermined significance and multiple myeloma using flow cytometric characteristics of plasma cells.

BACKGROUND AND OBJECTIVES: The differential diagnosis between multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) may be uncertain in some cases; this problem is reflected by discrepancies between different classification systems with an accordance in only 2/3 of cases. We studied whether flow-cytometric characteristics of plasma cells (PC) can be used for the differentiation between MGUS and MM. DESIGN AND METHODS: Patients were divided into 3 groups: Group A included 13 myeloma patients with a plasma cell infiltration of the bone marrow of 10-30%, serum M-protein < or = 3.5 g/dL (IgG) or < or = 2 g/dl (IgA) and without bone lesions in conventional radiography. Group B consisted of 53 patients who fulfilled the Durie and Salmon diagnostic criteria including at least one major criterion, and group C individuals with MGUS (n=17). The ratio of immunophenotypically normal (i.e. CD19(+)/CD56(-)) to all bone marrow plasma cells (BMPC), the number of peripheral blood PC (PBPC), the percentage of BMPC in S-phase and the DNA content of BMPC were analyzed. RESULTS: All individuals with MGUS and no patient with MM in group A or group B had a ratio of phenotypically normal to all BMPC > or = 20%. The median of monoclonal PBPC was 0/microL (range 0-2/ microL) in MGUS, 1/microL (range 0-30/microL) in MM group A and 2.4/microL (range 0-211/microL) in MM group B. The median percentage of BMPC in S-phase was 1.6% both in MGUS and in group A and 3% in group B. Aneuploidy was found in 12%, 11% and 41% in MGUS, group A and group B, respectively. INTERPRETATION AND CONCLUSIONS: The ratio of immunophenotypically normal to all BMPC was the only flow-cytometric parameter for the differentiation of MGUS and MM group A (p<0.0005). The other parameters were significantly different between MGUS and MM group B, but not group A.

Blood Cells↗
PubMed2001

Mucormycoses.

Over recent years the clinical importance of mucormycosis has significantly increased. Most frequently mucormycosis occurs in neutropenic patients with haematological diseases. It is caused by fungi of the order Mucorales. The clinical patterns of the disease produced by different genera or species of Mucorales are virtually identical. Rhizopus, Absidia, Rhizomucor and Mucor are the organisms most commonly isolated from patients who suffer from mucormycosis. Diagnosis of mucormycosis is difficult as it is based on culture methods or microscopy of clinical specimens. The diagnosis is often only made after a delay or even post-mortem. Therapy includes surgical intervention if possible and is based on systemic amphotericin B (conventional or liposomal).

Amphotericin B↗
PubMed2000

Neuropathy under chemotherapy.

Neuropathy is a dose-limiting side effect for a number of effective chemotherapeutic agents. A better understanding of effective mechanisms will lead to novel treatment strategies that will protect neurons without decreasing therapeutic efficacy. The assessment of the efficacy and neurotoxicity of various chemotherapeutic agents is vital, for a determination of the maximum allowable dose. The introduction of chemotherapy in the 50s and 60s of the twentieth century has resulted in the development of curative therapeutic interventions for patients with several types of solid tumours and hemopoietic neoplasms. The important obstacles encountered in the use of chemotherapy have been the toxicity to the normal tissue. During the past 8 years there has come about a new level of understanding of the mechanisms through which chemotherapeutic agents work. This has opened the door to new paradigms of treatment in which molecular, genetic, and biologic therapy can be used together to increase the sensitivity of abnormal cells to treatment, and to protect the normal tissues of the body from therapy-induced side effects. The implementation of new strategies could change the way therapy is delivered over the next few years and improve the outcome especially in patients with neoplasms that are currently resistant to conventional dose therapy.

Antineoplastic Agents↗
PubMed2000

[From laundry product to cancer drug--history of a drug class].

BACKGROUND: In recent years, the management of tumor-induced bone lesions has been fundamentally changed by the therapeutic class of the bisphosphonates. TUMOR-INDUCED HYPERCALCEMIA (TIH): This was the first oncological entity to be treated with bisphosphonates. Because of the impaired renal function that always accompanies TIH, bisphosphonates must be infused sufficiently diluted and over a period of 2 to 4 h in this indication. The success rate (normalisation of serum calcium levels) with pamidronate is > 90%. TUMOR-INDUCED OSTEOLYSIS (TIO): Intravenously administered bisphosphonates like pamidronate do not only significantly reduce the rate of complications from TIO, both in breast cancer and multiple myeloma, but they also frequently lead to a remission in bone (sclerosis of the lesion). For the modern amino-bisphosphonates a direct anti-tumoral effect could be shown, too. NEW DEVELOPMENTS: New bisphosphonates of the 3rd generation are under development. Zoledronat, a new chemical entity from Novartis, is currently the most potent bisphosphonate. Clinical studies have shown that zoledronate is significantly more effective than pamidronate in the treatment of HCM. CONCLUSION: Bisphosphonates are today an important part of the standard therapy of tumor-induced bone diseases. Due to their direct anti-tumoral effects, the modern drugs of this class play an increasing role also in the prevention of bone metastases.

Bone Neoplasms↗
PubMed2000

[New therapeutic approaches in advanced breast carcinoma. Palliative measures are increasingly more tolerable].

Advances in palliative chemotherapy are based on the development of new substances or new treatment strategies, such as, for example, high-dose chemotherapy. New cytostatic agents are developed with the aim of improving therapeutic efficacy and tolerability. Taxanes rapidly became part of standard treatment, and their combination with the anthracyclines represents the most effective treatment currently available. Liposomal encapsulation of anthracyclines can reduce their cardiotoxicity without loss of efficacy. Recent antimetabolites and the vinca alkaloid, vinorelbine, combine a good antitumoral effect with a favorable toxicity profile. The use of the monoclonal antibody, trastuzumab, has made specific immunotherapy possible for the first time. The role of high-dose chemotherapy remains uncertain, and further randomized studies are urgently needed.

Administration, Oral↗
PubMed2000

Increased expression of the tetraspanins CD53 and CD63 on apoptotic human neutrophils.

The recently discovered tetraspanin superfamily comprises a group of cell-surface proteins that are suggested to be involved in cell activation and signal transduction as well as in cell adhesion, motility, and metastasis. In this study, we have assessed the expression of two tetraspanins, CD53 and CD63, and two principal leukocyte adhesion molecules, CD11b and CD62L, on human apoptotic neutrophils. After aging of human neutrophils for 20 and 40 h in vitro, apoptosis was analyzed by light microscopy and flow cytometry. The binding of monoclonal antibodies directed against CD11b, CD62L, CD53, and CD63 on apoptotic and nonapoptotic cells was determined by dual-color flow cytometry. Aging of neutrophils in vitro resulted in a significant (P < 0.05) down-regulation of expression of the selectin CD62L, and a significantly increased expression of the two tetraspanins CD53 and CD63. The selective analysis of apoptotic versus nonapoptotic cells proved that both the increased expression of the tetraspanins and the loss of CD62L were restricted to the apoptotic subpopulation. An identical pattern of surface molecule expression was detected at 12 h after induction of apoptosis by an agonistic anti-Fas IgM monoclonal antibody. Further studies are required to clarify whether tetraspanins participate in the recognition of apoptotic circulating or extravasated neutrophils by macrophages.

Annexin A5↗
PubMed2000

Coincidence of Gaucher's disease due to a 1226G/1448C mutation and of an immunoglobulin G lambda multiple myeloma with Bence-Jones proteinuria.

We report about a 58-year-old female with coexisting type-I Gaucher's disease (GD) and multiple myeloma (MM). The diagnosis of GD was made in early childhood by means of bone marrow biopsy and was recently confirmed by analysis of the patient's genomic DNA for the underlying glucocerebrosidase mutations and the identification of the 1226G/1448C genotype. At the age of 24 years, the patient developed massive splenomegaly. Therefore, a splenectomy was performed. No further therapy was necessary for the next 34 years until 1999 when progressive anemia and thrombocytopenia occurred. Additional laboratory analysis revealed high serum protein and immunoglobulin (Ig) G levels and evidence of monoclonal gammopathy and lambda light-chain proteinuria, indicating plasma cell dyscrasia. This diagnosis was confirmed by the detection of osteolytic lesions in skeletal X-rays and a bone marrow biopsy showing an extensive infiltration with Gaucher cells and an increase of plasma cells, which expressed lambda light chains. When examined by means of electron microscopy, typical Gaucher cells, i.e., histiocytes containing tubular-structured cytoplasmatic material and spots of plasma cells with an increase of the endoplasmic reticulum, were found. GD associated with acquired MM has been described 13 times in the literature from 1968 to 1997. Only three of the patients were suffering from IgG myeloma. This distribution of the monoclonal component is in contrast to that of patients suffering from MM alone.

Bence Jones Protein↗
PubMed2000

Patients with malignant lymphomas experience a higher rate of documented infections than patients with breast cancer after high-dose chemotherapy with autologous peripheral stem cell transplantation.

The influence of underlying disease on documented infections has rarely been addressed in patients treated with high-dose chemotherapy (HDCT) and subsequent autologous peripheral blood stem cell transplantation (PBSCT). Because autografting has been used most frequently for malignant lymphomas and breast cancer, we analyzed in a retrospective study the data of 100 consecutive adult patients with either malignant lymphomas (group A, n = 50) or breast cancer (group B, n = 50) treated with HDCT at a single institution. The number of autografted CD34+ cells was not statistically different in either group. In this paper, we show for the first time that there is a significant difference in clinically or microbiologically documented infections in these groups of patients: documented infections occurred in 30% of malignant lymphoma patients but only in 4% of breast cancer patients (P=0.001). Of all isolated microorganisms, 78% were gram-positive. Because most of the documented infections were due to staphylococci, further studies should prospectively evaluate preventive measures to reduce the high incidence of these infections. This is especially important for lymphoma patients, who can be regarded as a high-risk group concerning gram-positive bacteremia.

Adult↗
PubMed2000

Bone marrow microvessel density is a prognostic factor for survival in patients with multiple myeloma.

The importance of neoangiogenesis for the progressive growth and viability of solid tumors is well established. Recently, there has been growing evidence that angiogenesis might also be important in hematological malignancies, but only few data are available. In this report, we have studied the impact of bone marrow microvessel density and survival in patients with multiple myeloma (MM). Immunohistochemical CD34 stained paraffin-embedded bone marrow biopsies of 44 patients with newly diagnosed MM were studied. Microvessels were counted in 400 x magnification and the mean number of vessels per area in each sample was noted as the microvessel density (MVD). The median MVD was 48 vessels/mm2, the range was 0-125 vessels/mm2. Using a cut-off value of the median MVD in the Kaplan-Meier analysis, the median survival was 22.2 months in the group with the higher MVD and was not reached in the group with the lower MVD (P< 0.01). In a multivariate Cox regression analysis, using previously identified prognostic factors beta2-microglobulin, C-reactive protein (CRP), and age, MVD remained significant as a prognostic factor (P< 0.03).

Adult↗
PubMed2000

New therapeutic approaches in primary systemic AL amyloidosis.

Primary systemic AL (amyloid light-chain) amyloidosis is a plasma cell disorder in which depositions of amyloid light-chain protein cause progressive organ failure. The prognosis of primary amyloidosis is generally poor, with a median survival of 1-2 years. There is no available treatment which improves impaired organ function by induction of amyloid mobilization. Since amyloidosis is a dynamic process, measures that reduce the supply of the amyloid fibril precursor protein can result in a major regression of the deposits. Conventional-dose melphalan can prolong the median duration of survival from 8.5 to 18 months, but the clinical response rates with improvement of impaired organ function are low and the response is slow. Preliminary data suggest that VAD is effective in AL amyloidosis. Up-front high-dose chemotherapy with autologous peripheral blood stem cell transplantation can result in an improvement of the patient's clinical condition, but the treatment-related toxicity can be high, owing to impaired organ function. The use of VAD followed by high-dose chemotherapy is the concept of a German trial. The improvement of the patient's condition prior to high-dose chemotherapy by induction of a remission with VAD might reduce the transplantation-related morbidity and mortality in amyloidosis.

Amyloid↗
PubMed2000

An unusual case of leukemic non-Hodgkin's lymphoma with blastic transformation.

We report on a patient who was diagnosed as having B-cell chronic lymphocytic leukemia (CLL) with atypical morphology. Flow cytometry disclosed CD5, CD19, and CD23 positivity, an immunophenotype seen mostly in B-CLL. Histology of the spleen and bone marrow suggested a diagnosis of small lymphocytic lymphoma. Upon blastic transformation, only 3 years after the diagnosis had been made, unusual clinical and laboratory features emerged. Lymphoid blasts appeared in the peripheral blood, and the patient developed nodular infiltrates consisting of these blasts at recent venous puncture sites. The patient did not respond to chemotherapy and died. The lymphoid blasts in the peripheral blood were CD5-, CD19+, and CD23+ and harbored t(11;14) (q13;q32) and t(11;21)(p11;q21) translocations. To account for the possibility of two independent lymphoid malignancies, molecular genetic analyses were performed on samples from the spleen, bone marrow and a lymph node with the large-cell lymphoma, which showed identical clones in these tissues. This unusual case supports the idea that in leukemic non-Hodgkin's lymphoma, in addition to morphology, an accurate diagnostic workup requires immunophenotypic, cytogenetic, and molecular studies.

CD5 Antigens↗
PubMed2000

Further evidence for oxidant-induced vascular endothelial growth factor up-regulation in the bronchoalveolar lavage fluid of lung cancer patients undergoing radio-chemotherapy.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent inducer of physiological and neoplastic blood vessel growth. Moreover, in vitro studies have demonstrated that VEGF can be up-regulated by conditions associated with the generation of free radicals and reactive oxygen species. In a previous study we reported on strongly increased VEGF concentrations in the bronchoalveolar lavage fluid (BALF) of patients with lung cancer under therapy. In this study we aimed to reveal whether this increase was due to the therapy-associated intrapulmonary oxidative burden. PATIENTS AND METHODS: A total of 103 BALF samples from 94 patients with lung cancer (82 patients with non-small-cell lung cancer, 12 patients with small-cell lung cancer) were studied at different times before, during or after cancer treatment. VEGF levels in the lavage fluid and ratios of oxidised methionine in proteins of epithelial lining fluid (ELF) were determined. RESULTS: As reported previously, strongly increased VEGF levels in the ELF were observed in patients undergoing chemotherapy when radiotherapy had been administered before. Increased levels of oxidised methionine indicated that these patients suffered from severe pulmonary oxidative stress that was significantly less in patients undergoing only chemotherapy. Similarly, VEGF concentrations in the ELF were significantly elevated in cancer patients at the time of diagnosis, but the oxidised methionine levels did not reveal significant oxidant/antioxidant imbalances in these patients. CONCLUSION: Systemic chemotherapy is associated with oxidative stress in vivo, which is more pronounced if patients are additionally treated with radiation. VEGF levels in the ELF are increased by this condition as well as by the activity of the tumour itself.

Adult↗