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Biomedical subjects

U Kaiser

Publications and source records attributed to U Kaiser.

At least 19 recordsLinked to original sources
PubMed2006

Incidence and risk factors of central nervous system recurrence in aggressive lymphoma--a survey of 1693 patients treated in protocols of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL).

BACKGROUND: Central nervous system (CNS) relapse is a devastating and usually fatal complication of aggressive lymphoma. The extent of the disease, the proliferation rate and the sites of extranodal involvement have been discussed as risk factors. We analyzed the patients treated on protocols of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL) between 1990 and 2000, evaluated the rate and prognostic factors for CNS recurrence and developed a risk model trying to identify subsets of patients suitable for future prophylactic strategies. PATIENTS AND METHODS: From 1993 to 2000, 1399 patients [ 60 years irrespective of LDH] were randomized to receive six cycles of combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-21, CHOP-14 or six cycles of CHOP+etoposide (CHOEP)-21, CHOEP-14 in a 2x2 factorial study design in the NHL-B1/B2 studies. From 1990 to 1997, 312 patients<or=60 years with an elevated LDH were randomized to five cycles CHOEP+involved field (IF) radiotherapy or three cycles CHOEP followed by high-dose BCNU, etoposide, cytarabine and melphalan (BEAM) and autologous stem-cell transplantation (NHL-A study). RESULTS: A total number of 1711 patients were initially eligible for this study, of whom 18 patients had to be excluded due to primary CNS involvement. In the remaining 1693 assessable patients, 37 cases of relapse or progression to the CNS (2.2%) were observed. The protocol asked for an intrathecal (i.th.) prophylaxis in patients with lymphoblastic lymphoma only (n=17), but overall 71 patients (71 of 1693=4.2%) received prophylaxis by decision of the treating physicians. Multivariate Cox regression analysis identified increased LDH (P<0.001) and involvement of more than one extranodal site (P=0.002) as independent predictors of CNS recurrence in the NHL-B1/B2 study population. Treatment with etoposide also evolved as a prognostic factor because the risk of CNS failure was significantly reduced after CHOEP (P=0.017). Elderly patients presenting with both an elevated LDH and lymphoma involvement in liver, bladder or adrenals had an up to 15-fold risk of spread of the disease to the CNS. CONCLUSION: The incidence of CNS relapse in 1693 patients treated for aggressive lymphomas on DSHNHL protocols from 1990 to 2000 was low (2.2%), although CNS prophylaxis was administered to <5% of patients. Thus, a general prophylaxis for all patients is not warranted, the less so since the effectiveness of i.th. prophylaxis itself is judged controversially. Increased LDH and involvement of more than one extranodal site were confirmed as independent risk factors. A cumulative 20% incidence of CNS disease in certain prognostic subgroups of elderly patients may render these candidates for i.th. prophylaxis; however, this approach would imply a potential overtreatment of approximately 80% of these patients deemed at high risk.

Adolescent↗
PubMed2006

Sequential high dose chemotherapy as initial treatment for aggressive sub-types of non-Hodgkin lymphoma: results of the international randomized phase III trial (MISTRAL).

INTRODUCTION: Sequential high dose (SHiDo) chemotherapy with stem cell support has been shown to prolong the event-free survival in patients with diffuse large B-cell lymphoma. METHODS: To confirm this result in a multicenter trial, we randomized patients with aggressive NHL, to receive either eight cycles of CHOP or SHiDo. The primary endpoint was overall survival. RESULTS: 129 evaluable patients were randomized to receive either CHOP or SHiDo: median age, 48 years; 62% male; stage III+IV: 73%; age adjusted International Prognostic Index 1/2/3: 21%/52%/27%. Toxicity grades 3+4 were more pronounced in the SHiDo-arm with 13% versus 3% of patients with fever; 34% versus 13% with infections; 13% versus 2% with esophagitis/dysphagia/gastric ulcer. The remission rates were similar in SHiDo and CHOP arms with 34%/37% complete remissions and 31%/31% partial remissions, respectively. After a median observation time of 48 months, there was no difference in overall survival at 3 years, with 46% for SHiDo and 53% for CHOP (P = 0.48). CONCLUSION: In this multicenter trial, early intensification with SHiDo did not confer any survival benefit in previously untreated patients with aggressive NHL and was associated with a higher incidence of grades 3/4 toxicity.

Adolescent↗
PubMed2005

On the peculiarities of CBED pattern formation revealed by multislice simulation.

A modified multislice method has been developed for calculations of Convergent Beam Electron Diffraction (CBED) patterns. The validity of the method for HOLZ- and Kikuchi-line calculations has been proofed by comparison to Bloch-wave calculations. The application of the method leads to the new understanding of CBED patterns formation. Dynamical scattering of weak HOLZ reflections plays the key role in the appearance of deficient lines in the central CBED disk. Different HOLZ lines do have significantly different and extended scattering areas; the central 000 CBED disk, consequently, contains structural information from an area around the primary beam which is determined by the Bragg angle of HOLZ reflections and the thickness of the sample. A variation of lattice parameters, if present within this area, results in artificial symmetry violations of the pattern and in changes of line profiles.

Journal Article↗
PubMed2004

[Azathioprine-associated myelodysplastic syndrome with cytogenetic aberrations].

HISTORY AND ADMISSION FINDINGS: A 49-years-old female with a history of multiple sclerosis and on medication with azathioprine over 5 years amounting to a cumulative dosage of 45 g presented with fatigue and sinus tachycardia. INVESTIGATIONS: Haematological analysis revealed a pancytopenia with a sustained normochromic anemia (hemoglobin 6,2 g/dl), a mild leukopenia (leucocytes 3500/ microl) and thrombocytopenia (platelets 22000/ microl) requiring platelet substitution. Bone marrow aspirate revealed a dysplasia of all three lineages with reduced thrombopoiesis and ineffective erythropoiesis. Cytogenetic analysis detected a complex aberrant clone including loss of the critically deleted regions in 5q31 and 7q31, as well as structural changes of 12p. The diagnosis was refractory cytopenia with multilineage dysplasia according to the WHO classification of myelodysplastic syndromes. TREATMENT AND COURSE: While allogeneic sibling transplantation was planned the patient developed spontaneous recurrent subdural haematoma and died due to persistent bleeding refractory to platelet substitution. CONCLUSION: Treatment with azathioprine may - depending on its cumulative dosage - lead to pancytopenia and subsequent development of myelodysplasia or secondary leukaemia, respectively. Complex genetic alterations involving chromosome 7 are characteristic. Long-lasting treatment with azathioprine needs critical assessment.

Anemia↗
PubMed2004

The formation of clusters and nanocrystals in er-implanted hexagonal silicon carbide.

Impurity atom cluster and nanocrystal formation in Er-implanted hexagonal SiC were studied using TEM and HAADF-STEM. Short interstitial loops were initially observed to form in the as-implanted layers. After annealing at 1600 degrees C extended matrix defects (wide interstitial loops and voids), Er atom clusters and nanocrystals grew. The wide interstitial loops act as strong sinks capturing diffusing dopants that gather first in lines, then planes, and finally in three-dimensional ErSi2 nanocrystals. The unstrained nanocrystals have a hill-like shape and only two polarity-dependent orientations with respect to the matrix. One-, two-, and three-dimensional Er atom clusters were also identified. For the case of Ge implantation, again the wide interstitial loops act as sinks for the implanted Ge, representing the seeds of the nanocrystal.

Carbon Compounds, Inorganic↗
PubMed2002

[AFP-producing adenocarcinoma of the stomach. A rare tumor with poor prognosis].

A 27-year-old, previously healthy man with abdominal discomfort was diagnosed with a small gastric tumor of the cardia by means of gastroscopy. Further staging revealed diffuse hepatic metastases and enlarged mediastinal lymph nodes. Serum alpha-fetoprotein (AFP) was grossly increased (7179 micro g/l). Biopsies taken from the gastric tumor and one of the hepatic metastases revealed a poorly differentiated adenocarcinoma (grade 3) with papillary and small solid areas and frequent clear cells. Cytoplasmic hyaline droplets were positive with PAS staining (diastase-resistant). Immunohistochemistry revealed focal tumor cells strongly positive for AFP and there was luminal expression of CEA. The diagnosis of an AFP-producing adenocarcinoma of the stomach was made. In spite of intensive combination chemotherapy the patient succumbed to his disease 3 months after diagnosis. The rare AFP-producing adenocarcinoma of the stomach is characterised by a distinct morphology and immunohistochemistry. A hepatoid differentiation may occur but is not obligatory as this case shows. In differential diagnosis, a metastasising germ cell tumor should be excluded. The prognosis for an AFP-positive adenocarcinoma is poor.

Adult↗
PubMed2002

Direct observation of defect-mediated cluster nucleation.

Ion implantation is widely used to introduce electrically or optically active dopant atoms into semiconductor devices. At high concentrations, the dopants can cluster and ultimately form deactivating precipitates, but deliberate nanocrystal formation offers an approach to self-assembled device fabrication. However, there is very little understanding of the early stages of how these precipitates nucleate and grow, in no small part because it requires imaging an inhomogenous distribution of defects and dopant atoms buried inside the host material. Here we demonstrate this, and address the long-standing question of whether the cluster nucleation is defect-mediated or spontaneous. Atomic-resolution illustrations are given for the chemically dissimilar cases of erbium and germanium implanted into silicon carbide. Whereas interstitial loops act as nucleation sites in both cases, the evolution of nanocrystals is strikingly different: Erbium is found to gather in lines, planes and finally three-dimensional precipitates, whereas germanium favours compact, three-dimensional structures.

Carbon Compounds, Inorganic↗
PubMed2001

Nanocrystal formation in hexagonal SiC after Ge+ ion implantation.

High-resolution and analytical electron microscopy techniques are used to characterize Ge-implanted hexagonal SiC. After annealing the implanted samples at 1200 degrees C, Ge is found to be located preferentially on interstitial sites. After annealing at 1600 degrees C, small nanocrystals of strained cubic and hexagonal (or faulted cubic) Ge and Ge Si form. Occasionally, hexagonal (or faulted cubic) Si nanocrystals are observed also.

Journal Article↗
PubMed2001

The structure of Si nanocrystals on SiC.

Si nanocrystals grown on cubic SiC have been characterized using high-resolution transmission electron microscopy. At lower temperatures nanocrystals grow in two different orientations, whereas at higher temperatures they grow in a single preferred orientation. The nanocrystals are shown to be unstrained; in some cases possibly due to the presence of a thin amorphous wetting layer.

Letter↗
PubMed2001

The role of cumulative physical work load in lumbar spine disease: risk factors for lumbar osteochondrosis and spondylosis associated with chronic complaints.

OBJECTIVES: To investigate the relation with a case-control study between symptomatic osteochondrosis or spondylosis of the lumbar spine and cumulative occupational exposure to lifting or carrying and to working postures with extreme forward bending. METHODS: From two practices and four clinics were recruited 229 male patients with radiographically confirmed osteochondrosis or spondylosis of the lumbar spine associated with chronic complaints. Of these 135 had additionally had acute lumbar disc herniation. A total of 197 control subjects was recruited: 107 subjects with anamnestic exclusion of lumbar spine disease were drawn as a random population control group and 90 patients admitted to hospital for urolithiasis who had no osteochondrosis or spondylosis of the lumbar spine radiographically were recruited as a hospital based control group. Data were gathered in a structured personal interview and analysed using logistic regression to control for age, region, nationality, and other diseases affecting the lumbar spine. To calculate cumulative forces to the lumbar spine over the entire working life, the Mainz-Dortmund dose model (MDD), which is based on an overproportional weighting of the lumbar disc compression force relative to the respective duration of the lifting process was applied with modifications: any objects weighing >or=5 kg were included in the calculation and no minimum daily exposure limits were established. Calculation of forces to the lumbar spine was based on self reported estimates of occupational lifting, trunk flexion, and duration. RESULTS: For a lumbar spine dose >9 x 10(6) Nh (Newton x hours), the risk of having radiographically confirmed osteochondrosis or spondylosis of the lumbar spine as measured by the odds ratio (OR) was 8.5 (95% confidence interval (95% CI) 4.1 to 17.5) compared with subjects with a load of 0 Nh. To avoid differential bias, forces to the lumbar spine were also calculated on the basis of an internal job exposure matrix based on the control subjects' exposure assessments for their respective job groups. Although ORs were lower with this approach, they remained significant. CONCLUSIONS: The calculation of the sum of forces to the lumbar spine is a useful tool for risk assessment for symptomatic osteochondrosis or spondylosis of the lumbar spine. The results suggest that cumulative occupational exposure to lifting or carrying and extreme forward bending increases the risk for developing symptomatic osteochondrosis or spondylosis of the lumbar spine.

Adult↗
PubMed2001

Haemolytic anaemia in a patient with anorexia nervosa.

We report on a 17-year-old female patient with severe anorexia nervosa (AN) (body mass index of 9.8 kg/m(2)) who developed hypophosphataemia (serum phosphate 0.4 nmol/l) and subsequent haemolytic anaemia during oral refeeding. Hypophosphataemia due to an increased phosphate uptake may lead to a reduction of erythrocyte adenosine triphosphate. This mechanism is important for the differential diagnosis of haemolytic anaemia in patients with AN. To prevent this complication, phosphate supplementation should be considered in the refeeding of severely malnourished patients.

Adenosine Triphosphate↗
PubMed2000

[Thalidomide as a new treatment option in patients with multiple myeloma]

Thalidomide as a new treatment option in patients with multiple myeloma. HISTORYAND ADMISSION FINDINGS: In a 56 year old woman the diagnosis of multiple myeloma of subtype IgG kappa led to the performance of an autologous stem cell transplantation. After initial partial remission the disease became refractory to standard chemotherapy requiring repeated plasmaphereses due to hyperproteinemia. INVESTIGATIONS: Before application of thalidomide the patient had a serum protein of 12 g/dl and a paraprotein of 4.4 g/dl. Bone marrow histology revealed a 40 % infiltration of the marrow by differentiated plasma cells. On neurologic examination a slightly diminished nerve conduction speed of the right median nerve due to carpal tunnel syndrome was diagnosed. TREATMENT AND COURSE: Treatment with thalidomide in a dosage of 400 mg p. o. was initiated and led to a partial remission with a > 50 % reduction of the paraprotein within four weeks. Due to a neuropathy (WHO grade 1) a dose reduction to 200 mg per day was performed after seven weeks of treatment. 48 weeks after initiation of treatment the patient remains in a stable partial remission with a paraprotein of 1.4 g/dl. After 20 weeks of treatment 5 % of the bone marrow remained infiltrated by monoclonal plasma cells. CONCLUSION: Monotherapy with thalidomide led to a stable partial remission in a patient with refractory multiple myeloma. In vitro thalidomide is a potent inhibitor of angiogenesis. Besides, a reduction of TNFalpha as well as an inhibition of cytokines have been described. The exact mechanism of the drug in multiple myeloma remains elusive. However several phase II trials have demonstrated a beneficial effect in relapsed or refractory disease. The optimal dosage and timing have to be studied in further trials.

Journal Article↗
PubMed1999

Redox-induced conformational changes in plastocyanin: an infrared study.

The conformational changes associated with the redox transition of plastocyanin (PC) were investigated by absorption and reaction-induced infrared spectroscopy. In addition to spectral features readily ascribed to beta and turn protein secondary structures, the amide I band shows a major component band at 1647 cm(-1) in both redox states of the protein. The sensitivity of this component to deuteration and increasing temperature suggests that PC adopts an unusual secondary structure in solution, which differs from those described for other type I copper proteins, such as azurin and halocyanin. The conformations of oxidized and reduced PC are different, as evidenced (1) by analysis of their amide I band contour and the electrochemically induced oxidized-minus-reduced difference spectrum and (2) by their different thermal stability. The redox-induced difference spectrum exhibits a number of difference bands within the conformationally sensitive amide I band that could be assigned to peptide C=O modes, in light of their small shift upon deuteration, and to signals attributable to side chain vibrational modes of Tyr residues. Lowering the pH to 4.8 induces destabilization of both redox states of the protein, more pronounced for reduced PC, without significantly affecting their secondary structure. Besides the conformational differences obtained at neutral pH, the oxidized-minus-reduced difference spectrum shows two broad and strong negative bands at 1405 and 1571 cm(-1), assigned to COO(-) vibrations, and a broad positive band at 1710 cm(-1), attributed to the C=O vibration of a COOH group(s). These bands are indicative of a protonation of (an) Asp or Glu side chain(s) upon plastocyanin oxidation at acidic pH.

Electrochemistry↗
PubMed1999

Successful salvage treatment for relapse after autologous stem cell transplantation in a patient with Hodgkin's disease--a case report.

We report a patient who relapsed 12 months after undergoing high-dose chemotherapy followed by autologous stem cell transplantation for refractory Hodgkin's disease, nodular sclerosis. The patient received sequential single-dose chemotherapy consisting of 140 mg/m2 epirubicin, 1.4 mg/m2 vincristine, and 50 mg/m2 prednisole on day 1, followed by 4000 mg/m2 cyclophosphamide on day 15 and 2000 mg/m2 etoposide on day 30. This regimen was given twice, predominantly on an outpatient basis without major toxicity. The patient reached a complete remission and has remained free of disease after an observation period of 48 months. Single-dose sequential treatment should be considered for refractory Hodgkin's disease, even for relapse after high-dose chemotherapy, as escalated single doses of cytostatic agents may overcome drug resistance.

Adolescent↗
PubMed1999

Origin of Threefold Periodicity in High-Resolution Transmission Electron Microscopy Images of Thin Film Cubic SiC.

: High-resolution transmission electron microscopy (HRTEM) images of the [1-10] zone of cubic SiC layers grown by molecular beam epitaxy (MBE) often reveal regions of material exhibiting an unusual threefold periodicity. The same contrast was found in earlier works of Jepps and Page, who attributed this contrast in HRTEM images of polycrystalline SiC to the 9R-SiC polytype. In this report we demonstrate by HRTEM image simulations that the model of the 9R polytype and an alternative twinning model can fit qualitatively the experimental HRTEM images. However, by comparing the fast Fourier transform (FFT) patterns of the experiments and the simulations, as well as by using dark-field imaging, we show unambiguously that only the model of overlapping twinned 3C-SiC crystals fully agrees with the experiments.

Journal Article↗
PubMed1999

Serum interleukin-6 has no discriminatory role in paraproteinaemia nor a prognostic role in multiple myeloma.

We determined interleukin-6 (IL-6) levels in the serum of 212 well-defined patients with newly diagnosed paraproteinaemia and evaluated its discriminatory value and prognostic role in multiple myeloma (MM). Results were compared with serum neural cell adhesion molecule and beta-2-microglobulin, both established prognostic MM markers. Paraproteinaemia-related diagnoses were: MM (60), other haematological diseases (46), solid tumours (35), autoimmune diseases (17) and monoclonal gammopathy of unknown significance (MGUS) (54). The range of IL-6 levels in all diagnostic groups overlapped widely and did not serve as a discriminatory marker in newly diagnosed paraproteinaemia even when patients with infection or fever (42) were excluded. In MM high IL-6 levels (>/= 50 pg/ml) were not associated with a shorter survival (P = 0.24). We compared our results with 20 published studies on serum IL-6 in paraproteinaemia and/or MM. IL-6 data have to be related to the assay used (bio- or immunoassay) and to the status of MM (newly diagnosed, during therapy, progressive disease). We conclude that serum IL-6 is not specific for paraproteinaemia-related diseases and will not serve as a reliable discriminatory or prognostic marker in paraproteinaemia and MM.

C-Reactive Protein↗
PubMed1999

Non-Hodgkin's lymphoma protocols in the treatment of patients with Burkitt's lymphoma and lymphoblastic lymphoma: a report on 58 patients.

Lymphoblastic lymphoma (LBL) and Burkitt's lymphoma belong to the very aggressive lymphomas requiring intensive therapy. We retrospectively analyzed 29 patients with Burkitt's lymphoma and 29 patients with LBL who received induction therapy with a CHOP-like lymphoma protocol. Patients with Burkitt's lymphoma (with a median age of 54.5 years) have a CR rate of 72% and a lymphoma free long-time survival of 55%. The International Prognostic Index was the most valuable prognostic factor for survival. Patients with LBL with a median age of 45 years had a CR rate of 55% and a lymphoma-free survival of 38%. Stage was the most predictive prognostic factor. Our data suggest that for older patients (>50) treatment with lymphoma protocols may yield response rates that are comparable to the results of patients with disseminated diffuse large cell lymphoma. Younger patients with risk factors should be treated with more intensive therapy like ALL-protocols. The role of auto-transplantation after high dose therapy (HDT) however as part of primary treatment still needs to be evaluated in clinical trials. One of four patients with LBL who received HDT and one of four patients with Burkitt's lymphoma who received HDT achieved long-term remission.

Adolescent↗