Search PubMed⌕ Search

Biomedical subjects

W Lange

Publications and source records attributed to W Lange.

At least 73 records · Page 4Linked to original sources
PubMed1997

Blood progenitor cell (BPC) mobilization studied in multiple myeloma, solid tumor and non-Hodgkin's lymphoma patients after combination chemotherapy and G-CSF.

For blood progenitor cell (BPC) mobilization, standard-dose VIP chemotherapy consisting of etoposide, ifosfamide and cisplatin has previously shown effective tumor reduction in solid tumor patients and sufficient progenitor cell mobilization for autologous blood cell transplantation. Mobilization chemotherapy regimens in multiple myeloma (MM) predominantly consist of melphalan or cyclophosphamide that induce marked cytopenia and considerable variability of progenitor cell collection. We studied whether in MM (n = 13), BPCs were efficiently and reproducibly mobilized with etoposide (500 mg/m2) and ifosfamide (1500 mg/m2), followed by daily s.c. G-CSF (5 micrograms/kg). In parallel, patients with solid tumors or non-Hodgkin's lymphomas (n = 28) treated with etoposide (500 mg/m2), ifosfamide (1500 mg/m2) and cisplatin (150 mg/m2) and identical dosing of G-CSF were analyzed. Before chemotherapy (day 0), on day 7 after chemotherapy and on days of leukapheresis (day 9-14), leukocyte numbers, mononuclear cells (MNCs), CD34+ cells and coexpression of lineage markers were analyzed. Median blood leukocyte numbers were 28,100/microliters (range, 19,600-40,400) on day 10 in myeloma patients and progressively declined over the next 4 days. In contrast, in solid tumor and lymphoma patients leukocyte numbers constantly increased from a median of 12,400/microliters (range, 6000-22,000) to 30,000/microliters (range, 16,300-63,300) between day 10 and day 13 after chemotherapy. Similar to leukocyte counts, median MNC numbers decreased in myeloma patients with successive leukaphereses, but steadily increased in solid tumor and lymphoma patients over the same period. CD34+ cell numbers in the blood peaked between day 9 and 11 (median: 40/microliters) in myeloma patients and then declined. In the solid tumor and lymphoma group, median CD34+ counts in the blood peaked on day 12 after mobilization chemotherapy (median: 100/microliters). The median CD34+ yield per leukapheresis in the myeloma group was 2.2 x 10(6)/kg (range, 1.5-4.7) on day 10, and fell steadily to 0.95 x 10(6)/kg on day 12, whereas in solid tumor/NHL patients median CD34+ cell yields remained between 3.5 and 3.7 x 10(6)/kg from day 10 to day 12 after mobilization chemotherapy (P < 0.001). To obtain sufficient cell numbers for engraftment a median of 2 (range, 1-3) mobilization chemotherapy cycles were needed in MM compared to 1 (range, 1-10) in solid tumor or lymphoma patients, with a median of 5 (range, 2-8) leukaphereses in MM compared to 1 (range, 1-10) (P < 0.05). Taken together, we found that for patients with MM, VP16 and ifosfamide efficiently and predictably mobilizes progenitor cells into the PB with > or = 3 x 10(6)/kg CD34+ cells collected after one to two mobilization chemotherapy cycles.

Adult↗
PubMed1997

High-dose chemotherapy with autologous peripheral blood stem cell transplantation for metastatic gastric leiomyosarcoma.

We report a case of metastatic gastrointestinal leiomyosarcoma treated with high-dose combination chemotherapy and autologous peripheral blood stem cell transplantation. After incomplete surgical resection, enteral, peritoneal and hepatic involvement remained. Postoperatively, standard-dose chemotherapy with etoposide, ifosfamide, cisplatin and epirubicine, and high-dose chemotherapy with the same agents (carboplatin replacing cisplatin) was given. Treatment was well tolerated and the patient remains in complete remission at 36+ months. We conclude that high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation may be of use as treatment for inoperable residual disease after resection of the primary lesion in gastrointestinal and other soft tissue sarcomas.

Adult↗
PubMed1997

Experimental gluing of lung parenchyma in rats.

Gelatin-resorcinol-dialdehyde adhesive has been developed from a gelatin-resorcinol-formaldehyde adhesive by replacing the formaldehyde with two less histotoxic dialdehydes, ethandial and pentandial. The aim of the present study was to evaluate the usefulness of this modified composition in gluing defects in lung parenchyma. In 40 male Wistar rats a standardized lung incision 1.0 cm in length and 0.8 cm in depth were closed by application of gelatin-resorcinol-dialdehyde adhesive. For macroscopic and microscopic examination 4 animals were sacrificed on each of postoperative days 2, 7, and 14 and 14 animals on each of postoperative days 28 and 120. Macroscopic examination revealed a tight closure of the parenchymal defects in all postoperative stages. Initially by an adhesive layer and later on by granulation tissue and scar tissue respectively. On microscopic examination an inflammatory tissue response with polymorphonuclear neutrophils and macrophages predominating was found 2 days postoperatively. After 7 days multinucleated giant cells appeared. On postoperative day 14 the tissue response presented a distinct granulomatous character with multinucleated giant cells persisting. After 28 days remnants of adhesive surrounded by granulation tissue were detectable. On postoperative day 120 the adhesive had been completely resorbed and the parenchymal defect was replaced by fibrous scar tissue. The gelatin-resorcinol-adhesive proved effective in tight closure of lung parenchyma in rats. The adhesive is resorbed completely and does not interfere with parenchymal healing.

Absorption↗
PubMed1997

Prospective evaluation of bone marrow signal changes on magnetic resonance tomography during high-dose chemotherapy and peripheral blood stem cell transplantation in patients with breast cancer.

RATIONALE AND OBJECTIVES: The authors evaluate bone marrow signal changes on magnetic resonance (MR) imaging during high-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT). METHODS: Fourteen patients with breast cancer without bone metastases underwent four sagittal MR imaging studies with T1-weighted, T2-weighted turbo spin-echo and inversion recovery sequences with short inversion time (STIR) of the lumbar spine: (1) during initial staging, (2) prior to high-dose chemotherapy after two cycles of induction chemotherapy, (3) early after PBSCT with a leukocyte exceeding 2000/microL, and (4) 6 to 8 weeks after PBSCT. Signal intensity ratios of averaged lumbar bone marrow to nucleus pulposus were measured and homogeneity was evaluated visually using a semiquantitative score. RESULTS: Compared with the initial finding (1): Signal intensity ratios were altered significantly at (2): T1-weighted: -22% +/- 14, P < 0.001; T2-weighted: -11% +/- 11, P < 0.01; STIR: +33% +/- 31, P < 0.01; Signal intensity ratios were altered significantly at (3): T2-weighted: -23% +/- 12, P < 0.001, STIR: -22% +/- 23, P < 0.01; and Signal intensity ratios were altered significantly at (4): only STIR: -16% +/- 19, P < 0.01. Homogeneity scores decreased at (3) for T1-weighted and STIR sequences (-1.6 +/- 0.5 to -2.0 +/- 0.7, P < 0.01 and -1.0 +/- 0.5 to -1.4 +/- 0.5, P < 0.01, respectively) and at (4) for the latter sequence (-1.0 +/- 0.5 versus -1.4 +/- 0.5, P < 0.01). At (4), T1-weighted images were less homogenous than initially in 3 of 14 (21%) patients. CONCLUSIONS: Magnetic resonance imaging demonstrates significant alterations of bone marrow composition during PBSCT but allows differentiation of benign therapy-related changes from those known in metastatic disease after completion of PBSCT.

Antineoplastic Agents↗
PubMed1997

Gradual development of organ damage in the murine zymosan-induced multiple organ dysfunction syndrome.

A well defined animal model is a prerequisite to test intervention strategies aimed at preventing the development of the multiple organ dysfunction syndrome. This study compares changes in clinical parameters to histopathologic changes in tissues, observed over a 12 day period after a single intraperitoneal injection of zymosan in C57BL/6 mice. Administration of zymosan induced gradual and progressive changes in wet and dry organ weight of the liver, kidneys, and particularly, lungs and spleen that correlated with increasing histopathology. From 6 days after zymosan injection onwards, hemorrhagic spots were found in the lungs evolving into massive hemorrhages at 12 days, when thickened interstitial walls and loss of the honey comb-like structures were observed. The liver displayed progressive accumulation of macrophage-like and mononuclear cells. After 12 days, numerous granuloma-like structures were disseminated throughout the liver parenchyma. The spleen displayed great changes in red and white pulp with increasing numbers of megakaryocytes and plasma-like cells. In the kidneys, necrosis of the tubular epithelium adjacent to granulomas on the ventral (peritoneal) side was found. In mice, a single intraperitoneal challenge with zymosan leads to progressive multiple organ damage, which becomes apparent at some time after the insult. This animal model displays a number of features encountered in human multiple organ dysfunction syndrome and appears suitable to conduct intervention studies.

Animals↗
PubMed1997

Comparative diagnostic accuracy of magnetic resonance imaging and immunoscintigraphy for detection of bone marrow involvement in patients with malignant lymphoma.

PURPOSE: To compare the diagnostic accuracy of magnetic resonance imaging (MRI) and immunoscintigraphy (IS) for detection of bone marrow infiltration in malignant lymphoma. PATIENTS AND METHODS: In 32 patients with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL), MRI of the axial skeleton and whole-body IS using technetium-99m (99mTc)-labeled monoclonal antibodies were reviewed and compared with iliac crest biopsies. Criterion for marrow infiltration was a positive biopsy or concordant positive results of MRI and IS. RESULTS: In 16 patients (50%), MRI, IS, and iliac crest biopsies were negative for marrow infiltration. Iliac crest biopsy showed infiltration in only four patients (13%). Infiltration was missed in two of 32 patients with IS and in one patient with MRI. In one additional patient, MRI was false-positive because of pelvic hematopoietic hyperplasia. A subset of nine patients (28%) with negative biopsies had bone marrow involvement according to MRI and IS with identical location and pattern of infiltration. In eight of these nine patients, diagnostic imaging indicated marrow involvement only in noncrest marrow. Subsequent biopsy confirmed infiltration in five patients. The clinical course suggested true-positive imaging results in the remaining four patients. Two patients (6%) remained equivocal. Overall concordance of MRI and IS for marrow infiltration was 88% (28 of 32 patients). CONCLUSION: Diagnostic imaging is essential for optimal staging in malignant lymphoma, as blind biopsies appear to have low sensitivity for bone marrow infiltration because of frequent involvement in noncrest marrow. both imaging modalities show a high rate of detection of bone marrow infiltration.

Adolescent↗
PubMed1997

[Small cell bronchial carcinoma and pleural empyema after pneumonectomy for tuberculosis].

We report the case of a 60-year-old man with a destructive ipsilateral bronchial carcinoma after pneumonectomy performed for tuberculosis several decades previously. The diagnosis steps in this case report are demonstrated and the correlations between the two diseases are discussed. The early diagnosis of malignant processes after thoracotomy performed because of tuberculosis is emphasized.

Carcinoma, Small Cell↗
PubMed1997

Prostatic neuroendocrine cells have a unique keratin expression pattern and do not express Bcl-2: cell kinetic features of neuroendocrine cells in the human prostate.

We investigated the keratin phenotype and bcl-2 immunoreactivity of neuroendocrine cells in the human prostate to determine whether the postmitotic status of these cells is associated with protection from apoptosis by bcl-2 protein expression and to elucidate the possible cell kinetic relationship between neuroendocrine cells and the other epithelial components of the prostate. Tissue specimens were selected from prostates of 19 patients harboring normal secretory glands (n = 15) and glandular benign prostatic hyperplasia (n = 10). Using a novel sequentially selective destaining immunoenzymatic cytochemical technique we were able to demonstrate the distribution of neuroendocrine cells, keratin markers identifying either basal, luminal, or intermediate cells, and the bcl-2 protein in single sections. Basal cell keratins were expressed in the minority of the neuroendocrine cells. In most of the cells, intermediate and luminal cell keratins were found and bcl-2 was constantly negative. Our findings indicate that neuroendocrine cells and other epithelial cells in the human prostate share a common keratin phenotype and probably originate from a common epithelial precursor. From the absence of bcl-2 we infer that the neuroendocrine cells have no progenitor cell characteristics.

Aged↗
PubMed1996

Basic innervation pattern and distribution of classic autonomic neurotransmitters in human nasal mucosal vasculature.

The neural control of human nasal vasculature is still not completely understood. This study was performed to demonstrate the innervation pattern of the different vessel types and to distinguish between nor-adrenergic and cholinergic structures. General innervation was demonstrated using antibodies to neuron-specific enolase and S-100 protein. Autonomic structures were shown by using antibodies to tyrosine hydroxylase and choline acetyltransferase (ChAT). In addition, choline acetyltransferase (AChe) histochemistry was performed. Nasal vasculature is controlled by a dense innervation that increases with the thickness of the tunica media. While all larger vessels show a mixed autonomic innervation, sympathetic structures seem to predominate in veins. These findings demonstrate that classic neurotransmitters play a major role in the regulation of nasal vasculature. The stronger innervation of arteries and cushion veins underlines their central position in the control of nasal air flow.

Adrenergic Fibers↗
PubMed1996

Volume shifts, unfolding and rolling of haustra in the isolated guinea pig caecum.

The large intestine extracts water from chyme and compacts chyme into faecal conglomerates; it is unclear what role the special pockets known as colonic haustra have in these events. Here we monitored the movements of haustra in isolated preparations of guinea pig caecum using videocamera and ultrasound and related them to contractions of muscle flaps and movements of glass beads in haustral pockets. We found that in partially filled caecal loops localized contractions of taeniae shift volume back and forth between adjacent haustra; volume unfolds haustral walls in a characteristic sweep with sequential intrahaustral folds popping out; cyclic contractions and relaxations of the fold then produce the caterpillar-like movement known as haustral rolling; ultrasound showed that haustral rolling made the haustral flow channel narrower and longer as haustral folds increase their height from 7.5 +/- 1.5 mm to 16 +/- 4 mm and their distance from 4.1 +/- 0.2 mm to 7.9 +/- 0.3 mm; luminal contents were alternatively shaken off the haustral wall, whirled around the lumen or left to settle. We also suspended the row of haustra between two taeniae inside a frame and attached flaps of taeniae and haustral folds to strain gauges to record their mechanical activity; both taeniae and haustral folds produced an undulating baseline tension; during rolling, folds produced phasic contractions at 17 +/- 2 cycles min-1 which propagated distally across haustral septa; rolling constantly shuffled around glass beads placed inside the haustra. When we stimulated the intramural nerves to the caecum through bipolar electrodes, all contractile activity was temporarily inhibited and haustral septa flattened; a rebound contraction then propagated aborally from the caecal pole and swept the glass beads ahead of it. Thus, tonic contractions of taeniae shift caecal contents back and forth across haustral septa; expansion of haustra triggers haustral rolling which shuffles contents; both these movements produce local flow within and between haustra which might enhance the separation of solid and liquid colonic contents.

Animals↗
PubMed1996

Biological and clinical advances in stem cell expansion.

One of the most exciting areas of hematological research is the ex vivo expansion of peripheral blood progenitor cells (PBPC). Several groups clearly demonstrated that the ex vivo expansion of hematopoietic progenitor cells is possible in the presence of various cytokine combination and/or different feeder layer models. This minireview summarizes recent developments in ex vivo expansion systems as well as first clinical applications.

Antigens, CD34↗
PubMed1996

Mobilization of peripheral blood progenitor cells for allogeneic transplantation: efficacy and toxicity of a high-dose rhG-CSF regimen.

Mobilization of PBPC was investigated in 19 healthy matched sibling donors using two different rhG-CSF regimens. Five donors (median age 39 years, range 17 to 57 years) received 10 micrograms rhG-CSF/kg bw once daily subcutaneously (s.c.), while 14 donors (median age 34 years, range 19 to 56 years) were treated with 10-12 micrograms rhG-CSF/kg bw twice daily s.c.. Leukapheresis was started on day 4 of rhG-CSF administration. Cytokine priming as well as collection of PBPCs were well tolerated. Application of twice daily rhG-CSF resulted in a higher yield of CD34+ cells in leukapheresis products than injection of once daily rhG-CSF. This high-dose twice daily rhG-CSF regimen is well tolerated and results in reliably high numbers of progenitor cells in the leukapheresis product in healthy donors, therefore collection as well as subsequent selection has been facilitated.

Adolescent↗
PubMed1996

Influence of Epstein-Barr virus latent gene expression on the apoptosis-inducing effects of cortisone and 2-chlorodeoxyadenosine (2-CDA) in B-cell lines.

Burkitt's lymphoma (BL) cell lines are heterogenous with regard to phenotype, growth characteristics, Epstein-Barr virus (EBV) latent gene and BCL-2 expression. Previously we have demonstrated that transfection with the EBV genes LMP or EBNA-2 upregulates BCL-2 in B-cell lines. In order to test the functional relevance of these findings, cell lines were examined with regard to their sensitivity towards different apoptosis-inducing agents. BL cell lines transfected with LMP expressed high levels of BCL-2, and were compared with the parental cell line expressing little or no BCL-2. We also studied EBV immortalized lymphoblastoid cell lines (LCL) with high BCL-2 expression and strong resistance towards low serum concentrations. Hydrocortisone (HC) and 2-chlorodeoxyadenosine (2-CDA) were used alone or in different combinations. Cell growth and apoptosis were studied morphologically and by determination of viability and DNA fragmentation. BL cell lines showed different sensitivity towards HC-induced apoptosis, and sensitive cell lines became more resistant towards HC after infection with EBV or transfection with LMP and subsequent upregulation of BCL-2 expression. BL cell lines and LCL were relatively insensitive towards 2-CDA-induced apoptosis, and high concentrations of 2-CDA were necessary, independently of the levels of BCL-2 expression. In contrast to low-grade non-Hodgkin's lymphomas, 2-CDA does not appear to be a valuable drug for the treatment of Burkitt's lymphoma. LMP expression provides resistance towards hydrocortisone-induced apoptosis in vitro, possible through upregulation of BCL-2.

Antineoplastic Agents↗