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J Eucker

Publications and source records attributed to J Eucker.

18 recordsLinked to original sources
PubMed2001

Relationship between bone marrow angiogenesis and plasma cell infiltration and serum beta2-microglobulin levels in patients with multiple myeloma.

There is growing evidence that angiogenesis is important not only in solid tumors but also in hematological malignancies. Recently, we found that bone marrow angiogenesis is a prognostic factor for disease-related survival in patients with multiple myeloma. In this report, we addressed the question of whether the microvessel density in bone marrow biopsies is correlated to other myeloma parameters, e.g., serum beta2-microglobulin (beta2-MG) and plasma cell infiltration in the bone marrow. In 22 multiple myeloma patients, immunohistochemical, CD34-stained, paraffin-embedded bone marrow biopsies before and after chemotherapy were studied. Microvessels were counted in 400x magnification, and the mean number of vessels per area in each sample was noted as the microvessel density (MVD). Pretreatment bone marrow MVD (median: 44, range: 11-175 vessels/mm2) correlated significantly with the bone marrow plasma cell infiltration (median: 30%, range: 5-90%, r = 0.642, P=0.001) and beta2-MG (median: 2.74, range: 1.4-26.1 mg/l, r = 0.749, P < 0.0005). In contrast, there was no correlation between posttreatment MVD and plasma cell infiltration or beta2-MG (median: MVD 31, range: 0-221 vessels/mm2, median plasma cell infiltration: 15%, range: 5-80%, r = 0.229, P = 0.306 and median beta2-MG: 2.65, range: 1-27.6 mg/l, r = -0.042, P = 0.853). These findings show that the strong correlations between bone marrow MVD and plasma cell infiltration as well as serum beta2-MG levels disappear after chemotherapy. The underlying mechanisms need further investigations.

Biopsy↗
PubMed2001

Achievement of complete remission in refractory Hodgkin's disease with prolonged infusion of gemcitabine.

Although, in recent decades effective chemotherapy regimens have been developed for the treatment of Hodgkin's disease, the prognosis of patients who experience disease progression is still very poor. New treatment approaches are urgently required to salvage such patients. In a patient with Hodgkin's disease who failed to achieve complete remission with the escalated BEACOPP protocol, progression with bone marrow infiltration and B symptoms developed despite further treatment. Subsequently, gemcitabine was administered in a novel schedule as a four-hour infusion of 250 mg/m2 on days 1, 8, and 15, every four weeks. After the first cycle, the dose was reduced to 200 mg/m2 because of grade 3 neutropenia. The condition of the patient improved after the second cycle and no toxicity was observed during cycles 3-6. Complete remission was achieved. Two years after the end of gemcitabine therapy, the patient is in good clinical condition and in continuous complete remission without further treatment. This is the first report of the prolonged infusion of gemcitabine as a salvage therapy in Hodgkin's disease.

Adult↗
PubMed2001

Serum levels of the angiogenic cytokines basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in multiple myeloma.

Angiogenesis is a crucial process in growth and progression of cancer and there is growing evidence that neovascularisation is important in hematological malignancies. Since an increased angiogenic potential has been identified in multiple myeloma, we simultaneously measured circulating serum levels of the cytokines bFGF, VEGF, HGF and IL-6 by ELISA in 67 patients with multiple myeloma or monoclonal gammopathies of undetermined significance (MGUS) and in 20 controls. Median values of bFGF were 4.7 pg/ml in healthy volunteers, 6.2 in MGUS, 6.3 in myeloma stage I, 13.4 in stage II and 21.7 in stage III. Myeloma patients had significantly higher bFGF serum levels than controls (p<0.001). Pretreatment bFGF levels differed significantly in the Salmon and Durie stages I-III (p=0.02) and were significantly elevated in stage II-III compared to stage I myeloma (p=0.02). In patients responding to chemotherapy according to the CLMTF criteria, a significant decrease in serum bFGF, VEGF and HGF levels occurred (median pretreatment values for bFGF 23.9 pg/ml, post-treatment 6.5 pg/ml; p<0.001, for VEGF 223 pg/ml versus 105 pg/ml; p=0.02 and for HGF 1429 pg/ml versus 1077 pg/ml; p=0.02, respectively). In 11 patients who did not achieve a remission, there was no significant decrease in bFGF, VEGF and HGF levels. These data show that myeloma in stages II and III is associated with an increase in serum bFGF concentrations and give the first report that effective chemo-therapy is accompanied by a significant decrease in the angiogenic factors bFGF, VEGF and HGF, while no decrease of these factors could be found in nonresponders.

Adult↗
PubMed2001

Decrease of bone marrow angiogenesis in myeloma patients achieving a remission after chemotherapy.

The impact of angiogenesis is well known for the growth and viability of solid tumors. Fewer studies have been published relating angiogenesis to clinical or pathological parameters in hematological malignancies. In this report, we have estimated the bone marrow microvessel density (MVD) before and after conventional-dose or high-dose chemotherapy with autologous stem cell transplantation. Immunohistochemical CD34-stained paraffin-embedded bone marrow biopsies of 21 patients with stage III multiple myeloma were studied. Microvessels were counted at 400x magnification, and the mean number of vessels per area in each sample was noted as the MVD. The median MVD of all patients was 53.1 vessels/mm2 (range 15.5-174.7 vessels/mm2) before treatment and 29.3 vessels/mm2 (range 0-221.1 vessels/mm2) after chemotherapy. The post-treatment MVD in the two groups of patients with and without remission was significantly different (p=0.001), whereas the pretreatment MVD was not. Responders but not nonresponders showed a significant decrease of MVD after therapy in comparison to their pretreatment levels. The progression-free survival in patients who achieved a reduction in MVD after chemotherapy was significantly longer than in patients without a decrease in MVD (P=0.006). Furthermore, we compared the MVD of patients after achievement of a remission to MVD of 15 untreated stage I myeloma patients. The MVD of patients in remission was not statistically different from the MVD in stage I myeloma. These results underscore the impact of angiogenesis in myeloma and give the first report that effective chemotherapy is accompanied by a significant decrease in bone marrow angiogenesis in this disease.

Aged↗
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

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

Arterial thrombosis associated with anticardiolipin and anti-beta2-glycoprotein-I antibodies in patients with non-Hodgkin's lymphoma: a report of two cases.

Autoimmune phenomena in lymphoid malignancies are often observed. However, clinical manifestations such as a secondary antiphospholipid syndrome in the presence of antiphospholipid antibodies are rarely reported. Furthermore, in the few cases of lymphomas so far reported with thrombosis associated with elevated antiphospholipid antibodies, the anti-beta2-glycoprotein-I antibodies have not been studied. We report on two cases of arterial thrombosis occuring in patients with B-cell lymphoma who presented with positive anticardiolipin and anti-beta2-glycoprotein-I antibodies. Our observation suggests that patients with non-Hodgkin's lymphoma and both anticardiolipin and anti-beta2-glycoprotein-I antibodies may be, similar to lupus patients, at considerable risk towards thrombosis, especially towards arterial thrombosis.

Aged↗
PubMed2000

Novel approaches to the treatment of primary amyloidosis.

Primary (AL, amyloid light-chain) amyloidosis is a plasma cell disorder in which deposits of amyloid light-chain protein cause progressive organ failure. It is important to recognise that amyloidosis is a dynamic process and chemotherapy-induced reduction of the activity of the plasma cell clone reduces the supply of the amyloid precursor protein and can result in a major regression of the deposits. The most common target organ is the kidney and renal amyloidosis manifests as proteinuria or nephrotic syndrome. Proteinuria is seen in three quarters of patients. Amyloid related nephrotic syndrome and renal failure are potentially reversible. Fatigue, congestive heart failure, hepatomegaly, peripheral neuropathy, orthostatic hypotension, carpal tunnel syndrome and macroglossia are other common features. The median survival is one to two years. Conventional-dose melphalan as standard treatment can prolong the median duration of survival by about ten months, but the clinical response rates with improvement of impaired organ function are low. Up-front high-dose chemotherapy with autologous peripheral blood stem cell transplantation is much more effective and can result in a major improvement in the clinical condition of patients. However, the toxicity related to this treatment can be relevant due to impaired organ function. Conventional-dose chemotherapy consisting of vincristine, doxorubicin and dexamethasone or high-dose dexamethasone or interferon-alpha are other possible approaches to treatment. The improvement of patient condition with an effective conventional-dose chemotherapy may increase the tolerability of high-dose chemotherapy and reduce transplantation related problems.

Amyloidosis↗
PubMed2000

Pregnancy-induced hypertension and duration of sexual cohabitation.

OBJECTIVE: To evaluate the possible association between duration of sexual cohabitation and the risk of pregnancy-induced hypertension (PIH). STUDY DESIGN: A matched case-control design in which each case of PIH was compared with three controls. Information was obtained about use of barrier contraception, duration of intercourse prior to pregnancy and paternity. RESULTS: Sixty-eight cases were included in the study. For primiparous women, a shorter duration of sexual cohabitation without contraception was associated with a small and nonsignificant risk of PIH. For multiparous women, a greater length of time since stopping use of barrier contraception was associated with a greater risk of PIH. CONCLUSION: Advising nulliparous women to prolong the duration of sexual cohabitation prior to conception in an effort to decrease the risk of PIH is not justified, based on the findings of this study.

Adult↗
PubMed2000

Diagnosis and treatment of AL amyloidosis.

AL (amyloid light-chain) amyloidosis is a plasma cell disorder in which depositions of amyloid light-chain protein cause progressive organ failure. Virtually all patients with AL amyloidosis have a monoclonal protein in the serum or urine or a monoclonal population of plasma cells in the bone marrow. The most common target organ is the kidney and renal amyloidosis manifests as proteinuria or nephrotic syndrome in 3/4 of the patients. The median survival is one to two years. It is important to recognize that the amyloidosis is a dynamic process, and chemotherapy induced reduction of the activity of the plasma cell clone reduces the supply of the amyloid precursor protein and can result in a major regression of the deposits. Amyloid-related nephrotic syndrome and renal failure are potentially reversible. Conventional-dose melphalan as standard treatment can prolong the median duration of survival about 10 months, but the clinical response rates with improvement of impaired organ function are low with a slow response. Upfront high-dose chemotherapy with autologous peripheral blood stem cell transplantation is much more effective and can result in a major improvement of the patient's clinical condition, but the treatment-related toxicity can be relevant due to impaired organ function. The initial use of a conventional-dose chemotherapy consisting of vincristine, doxorubicin and dexamethasone (VAD) to achieve a remission and subsequent high-dose chemotherapy is the concept of a German trial. The improvement of the condition of the patient by this approach may increase the tolerability of high-dose chemotherapy and reduce transplantation-related problems.

Amyloid↗
PubMed1999

Rapid reversal of nephrotic syndrome due to primary systemic AL amyloidosis after VAD and subsequent high-dose chemotherapy with autologous stem cell support.

In a patient with nephrotic syndrome, renal biopsy revealed AL amyloid deposits. Monoclonal lambda light chains were identified in serum and urine. A low percentage of monoclonal plasma cells was detected in the bone marrow. The patient received four cycles of VAD and subsequent high-dose chemotherapy (HDCT) with melphalan (200 mg/m2) followed by autologous peripheral blood stem cell transplantation. Proteinuria rapidly diminished during chemotherapy. Three months after HDCT, the patient has no edema, and no signs of plasma cell dyscrasia are currently detectable. Using VAD before starting HDCT may improve the condition of patients with amyloidosis and reduce transplantation-related morbidity and mortality.

Amyloidosis↗
PubMed1999

Contaminations occurring in fungal PCR assays.

Successful in vitro amplification of fungal DNA in clinical specimens has been reported recently. In a collaboration among five European centers, the frequency and risk of contamination due to airborne spore inoculation or carryover contamination in fungal PCR were analyzed. The identities of all contaminants were specified by cycle sequencing and GenBank analysis. Twelve of 150 PCR assays that together included over 2,800 samples were found to be contaminated (3.3% of the negative controls were contaminated during the DNA extraction, and 4.7% of the PCR mixtures were contaminated during the amplification process). Contaminants were specified as Aspergillus fumigatus, Saccharomyces cerevisiae, and Acremonium spp. Further analysis showed that commercially available products like zymolyase powder or 10x PCR buffer may contain fungal DNA. In conclusion, the risk of contamination is not higher in fungal PCR assays than in other diagnostic PCR-based assays if general precautions are taken.

Acremonium↗
PubMed1997

[Involvement of secretory Candida proteinases in the adherence of C. tropicalis blastoconidia in a cell culture model].

The influence of the heterologous acid secretory Candida proteinases on the adherence of the non-proteinase secreting strain of C. tropicalis DSM 4959 to epitheloid cells (vero line) was examined. The proteinases of the following Candida strains were used: C. albicans ATCC 10261 (serotype A), C. albicans ATCC 48867 (serotype B), C. tropicalis DSM 4238. The assays were performed with the previously described in-vitro-adherence test [1] using the following principle steps: Candida proteinases and C. tropicalis blastoconidia were incubated with verocells in microtest plates in phosphate-buffer in the range of pH 4.0 to pH 7.0. Adherent Candida cells were detected according to Filler et al. [2] with anti-Candida-mannoprotein antibodies and a secondary anti-rabbit-peroxidase conjugate. Compared to controls with denaturated proteinases, the photometric evaluation of adherent C. tropicalis cells showed, under optimal conditions, an augmentation of the adherence due to the Candida proteinases of about 50%. The optimum of this adherence augmentation was in the range of pH 5.5 which is outside the general activity optimum of Candida proteinases (pH 3). The degree of purity of these proteinases had no marked influence on the adherence. The specificity of the proteinase dependent adherence augmentation could be demonstrated with the enzyme inhibitor Pepstatin A. C. tropicalis blastoconidia supplemented by pepstatin A and active Candida proteinase adhered in the same range as with denaturated proteinases in control tests. Our results suggest a function of Candida proteinases in the adherence process of blastoconidia to epithelia.

Animals↗
PubMedDate not supplied

Disseminated mucormycosis caused by Absidia corymbifera leading to cerebral vasculitis.

An 18-year-old woman was admitted to hospital because of subcutaneous hematoma and fever of unknown origin. Acute myeloid leukemia was diagnosed and empirical antimicrobial treatment and induction chemotherapy were started. After initial defervescence, fever relapsed 2 days after the onset of neutropenia. The CT scan of the lung was consistent with an invasive fungal infection. Treatment with amphotericin B was started and antimicrobial treatment was continued with liposomal amphotericin B because of an increase in creatinine later. The fever persisted and the patient suddenly developed progressive neurological symptoms. CT scan of the head suggested cerebral infarction and angiography of the extra- and intracranial arteries showed signs of vasculitis. Six days after the onset of neurological symptoms cerebral death was diagnosed. Autopsy revealed non-septate, irregularly branched hyphae in various histologic sections including brain. Absidia corymbifera could be isolated from lung tissue confirming the diagnosis of disseminated mucormycosis. In this case, angiographic findings suggested severe cerebral vasculitis which was in fact caused by thromboembolic dissemination of fungal hyphae. This case underlines the fact that cerebral symptoms in febrile neutropenic patients are highly indicative for fungal infections of the brain.

Absidia↗