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Biomedical subjects

R Weide

Publications and source records attributed to R Weide.

At least 19 recordsLinked to original sources

[Lymphomas: new therapeutic options].

Malignant lymphomas are differentiated clinically, morphologically and molecular-biologically, into aggressive (formerly high-grade malignant) and indolent (formerly low-grade malignant) lymphomas. In the meantime, virtually all patients can be diagnosed and treated on an ambulatory basis. The introduction of the monoclonal antibody rituximab (R) in combination with chemotherapeutic agents, has led to the development of highly potent forms of chemoimmunotherapy. In the case of aggressive lymphomas, R-CHOP has been shown to be significantly superior to CHOP alone, both in elderly and younger patients. In stage III and IV indolent (follicular) lymphomas, rituximab/chemotherapy combinations achieve response rates in excess of 90%, and prolonged progression-free survival rates which, for the first time hold out hope of a cure. Monoclonal antibodies that can be coupled to radioisotopes open up new possibilities for potent radioimmunotherapy which look promising for effecting a cure or long-lasting palliation in additional proportion of the patients.

Antineoplastic Combined Chemotherapy Protocols↗

High affinity recognition of a Phytophthora protein by Arabidopsis via an RGD motif.

The RGD tripeptide sequence, a cell adhesion motif present in several extracellular matrix proteins of mammalians, is involved in numerous plant processes. In plant-pathogen interactions, the RGD motif is believed to reduce plant defence responses by disrupting adhesions between the cell wall and plasma membrane. Photoaffinity cross-linking of [125I]-azido-RGD heptapeptide in the presence of purified plasma membrane vesicles of Arabidopsis thaliana led to label incorporation into a single protein with an apparent molecular mass of 80 kDa. Incorporation could be prevented by excess RGD peptides, but also by the IPI-O protein, an RGD-containing protein secreted by the oomycete plant pathogen Phytophthora infestans. Hydrophobic cluster analysis revealed that the RGD motif of IPI-O (positions 53-56) is readily accessible for interactions. Single amino acid mutations in the RGD motif in IPI-O (of Asp56 into Glu or Ala) resulted in the loss of protection of the 80-kDa protein from labelling. Thus, the interaction between the two proteins is mediated through RGD recognition and the 80-kDa RGD-binding protein has the characteristics of a receptor for IPI-O. The IPI-O protein also disrupted cell wall-plasma membrane adhesions in plasmolysed A. thaliana cells, whereas IPI-O proteins mutated in the RGD motif (D56A and D56E) did not.

Amino Acid Motifs↗

Outpatient therapy in metastatic breast cancer. A retrospective study of 90 patients treated in an oncology group practice.

BACKGROUND: Whenever possible, treatment of breast cancer should be performed in an outpatient setting, but only few data about patients being treated exclusively on an outpatient basis are available. PATIENTS AND METHODS: A retrospective analysis was performed in 90 unselected patients who were treated consecutively in our oncology group practice between 6/95 and 8/99. RESULTS: Median age at detection of metastases was 55 years (30-90) and performance status ranged from 0 to 2. 83 patients (92.2%) received chemotherapy, 7 (7.8%) received endocrine therapy only. CMF was used in 27.7%, anthracyclines in 71.1% and taxanes in 43.3%. 855 chemotherapy cycles were performed and the observed toxicity was mild. Reversible grade 3 and 4 hematotoxicity was seen after 27 cycles (3.2%). Neurotoxicity or mucositis grade 3 and 4 were seen in 6 patients (6.6%). Therapy-associated hospitalization occurred in 1 patient thrice due to febrile neutropenia. Complete remissions were seen in 5 patients (5.6%) during first-line therapy. Median survival of the whole cohort until the end of the follow-up period (2/03) was 28 months (2-259). Overall survival after 1, 2, 3 and 5 years was 83, 56, 33 and 18% respectively. 50% could die at home. CONCLUSIONS: Treatment of metastatic breast cancer can be performed with minimal toxicity and a high patient acceptance in the outpatient setting. Overall survival and median survival are comparable to historical results achieved in specialized academic hospitals. Hospitalization could be avoided in the majority of patients and half of them could die at home.

Adult↗

[Severe lead poisoning due to Ayurvedic indian plant medicine].

HISTORY AND CLINICAL FINDINGS: A 39-year-old woman with a history of slowly progressive muscular dystrophia was transferred to us for further evaluations of a hypochromic, microcytic anaemia. The patient complained about progressive muscle weakness, loss of appetite and constipation, sleep disorders as well as muscle and back pain. Clinical examination revealed a tetraparesis without any detectable muscle reflexes and atrophic muscles of the extremities. A bilateral radial paresis was found with a loss of power. INVESTIGATIONS: She presented with a hypochromic, microcytic anaemia with a haemoglobin of 7.9 g/dl. Re-evaluation of her peripheral blood smear showed basophilic stippling of the erythrocytes. Bone marrow biopsy revealed a marked dyserythropoiesis with 50% ring sideroblasts. After the examination of the bone marrow, the blood lead level was found to be grossly elevated up to 880 microg/l. DIAGNOSIS: Re-evaluation of the patient's history revealed that she had been to India for an Ayurvedic treatment approach to improve her muscle dystrophia. She had taken regularly 4 different natural plant pills which she had bought in an Ayurvedic health centre. Toxicologic analysis of these pills revealed one to have a lead concentration of 50.4 mg/g. TREATMENT AND COURSE: The patient was treated with 16 infusions of sodium-EDTA followed by a 4-week treatment with dimercaptopropionic acid orally. Her neurological condition improved and the radial paresis resolved gradually so that she could return to work. Her haematological parameters normalized. CONCLUSION: This case report underscores the importance, while asking patients for their drug history, to ask additionally if natural plant medicine is taken or applied regularly. The report reveals that Ayurvedic pills from India may have a high concentration of lead and may cause severe poisoning.

Adult↗

Successful long-term treatment of systemic lupus erythematosus with rituximab maintenance therapy.

Systemic lupus erythematosus (SLE) is a chronic, inflammatory autoimmune disease that may involve multiple organ systems. Treatment consists of immunosuppression, cytotoxic treatment, plasmapheresis and immunoglobuline therapy. Treatment of patients refractory to standard treatment approaches is difficult and results are poor. We describe a 39-year old patient with SLE suffering from grand mal epilepsy due to cerebral vasculopathy with positive lupus anticoagulant, who was refractory to standard treatment modalities. The patient was treated with the anti-CD20 monoclonal antibody rituximab (375 mg/m2 x 4, repeated at weekly intervals). Rituximab applications were delivered in October 2000, March 2001 and October 2001. Since March 2002 she has received maintenance therapy with rituximab 375 mg/m2 every three months. A second female with refractory SLE was treated successfully in April 2002 and receives maintenance therapy every three months. Both patients responded well to rituximab therapy. The first patient showed a major improvement of her clinical condition, and 30 months after the beginning of the rituximab therapy she is free of any symptoms. Inflammation parameters, ANA and lupus anticoagulant declined significantly after the treatment. The clinical condition of the second patient improved dramatically, all inflammation parameters normalized and her circulating immunocomplexes disappeared. In conclusion, rituximab maintenance treatment may be a new effective therapy in SLE.

Adult↗

Dose reduction of steroid premedication for paclitaxel: no increase of hypersensitivity reactions.

BACKGROUND: Premedication with dexamethasone, ranitidine and clemastine is mandatory for patients receiving paclitaxel to avoid hypersensitivity reactions. The proposed dexamethasone dose is 20 mg orally 12 and 6 h prior to paclitaxel infusion. With this premedication severe hypersensitivity reactions are reduced to 1-2% of the treated patients. Besides this oral schedule a single dose of dexamethasone, 40 mg given i.v., just prior to paclitaxel has been shown to be equally effective. In an attempt to reduce steroid-induced side effects, especially for patients receiving weekly paclitaxel protocols, we reduced the dexamethasone dose. PATIENTS AND METHODS: A total of 132 patients were treated on an outpatient basis with paclitaxel-containing protocols. Paclitaxel was given in doses of 135-175 mg/m(2) once every 3 weeks in 76 patients and/or with 100 mg/m(2) weekly in 70 patients. Dexamethasone premedication was given in a single dose (40, 20, 10 mg) as an infusion directly before paclitaxel. RESULTS: 0/46 patients receiving 40 mg dexamethasone premedication in 235 cycles and 0/48 patients receiving 20 mg dexamethasone premedication in 186 cycles experienced a severe hypersensitivity reaction. 1/52 patients receiving 10 mg dexamethasone in 480 applications developed a severe hypersensitivity reaction with bronchospasm, hypotension and supraventricular tachycardia shortly after her first paclitaxel infusion started. CONCLUSION: No increase of severe hypersensitivity reactions is seen when dexamethasone premedication is reduced to doses of 20 or even 10 mg prior to paclitaxel infusion.

Adult↗

The polyneuropathy associated with Waldenström's macroglobulinaemia can be treated effectively with chemotherapy and the anti-CD20 monoclonal antibody rituximab.

A 50-year-old male developed headache, impaired balance, visual defects and severe deafness. Ten months later he presented with markedly reduced power and tremor of his right arm. Waldenström's macroglobulinaemia (WM) with accompanying polyneuropathy was diagnosed. The patient received chemotherapy, which resulted in a partial improvement of the arm tremor. Subsequently, he was treated with rituximab (4 x 375 mg/m2), leading to complete resolution of the tremor and the paresis of his arm. Additionally, his headache and imbalance disappeared. Fifteen months after rituximab therapy he remained free of any neurological symptoms. This is the first report showing that WM-associated polyneuropathy can be treated effectively with a combination of chemotherapy and the anti-CD20 monoclonal antibody rituximab.

Antibodies, Monoclonal↗

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↗

Induction of complete haematological remission after monotherapy with anti-CD20 monoclonal antibody (RITUXIMAB) in a patient with alkylating agent resistant Waldenström's macroglobulinaemia.

Response of Waldenström's macroglobulinaemia to chemotherapy with alkylating agents is usually only transient. We report a case with marked bone marrow involvement and resistance to chemotherapy with alkylating agents. The patient was red cell and platelet transfusion dependent. Three weeks after rituximab-monotherapy, he achieved a complete haematological remission which is continuing 6 months after the end of therapy. Our case demonstrates that treatment with the unconjugated anti-CD20-monoclonal antibody (rituximab) may be a new powerful tool for a better treatment of Waldenström's macroglobulinaemia.

Aged↗

Paracentromeric sequences on tomato chromosome 6 show homology to human satellite III and to the mammalian CENP-B binding box.

In order to isolate centromeric sequences from tomato (Lycopersicon esculentum) chromosome 6, a large-scale RAPD screen was performed. Among 1500 polymorphic RAPD markers tested, 100 were identified as chromosome 6-specific, using a L. esculentum substitution line carrying chromosome 6 from L. pennellii. Fifty-seven of these markers proved to originate from L. pennellii, and of these, 13 were genetically mapped between the morphological markers yellow virescent (yv) and thiaminless (tl), which flank the centromere. These markers could be assigned to three genetic loci, with 11 of the markers mapping to a single locus. Further resolution of this cluster was achieved using radiation-induced deletions that removed yv or tl but not the centromere. Seven markers were shown to be located outside all of the deletions. These seven markers and three of the other markers of the cluster were cloned and sequenced. Five of the clones are present as single-copy or low-copy-number sequences and five represent middle repetitive sequences. Three sequences show homology to the mammalian CENP-B binding box; clone AG12 contains two of these boxes and also shows homology to human satellite III.

Autoantigens↗

Induction of defense-related responses in Cf9 tomato cells by the AVR9 elicitor peptide of cladosporium fulvum is developmentally regulated

The AVR9 elicitor from the fungal pathogen Cladosporium fulvum induces defense-related responses, including cell death, specifically in tomato (Lycopersicon esculentum Mill.) plants that carry the Cf-9 resistance gene. To study biochemical mechanisms of resistance in detail, suspension cultures of tomato cells that carry the Cf-9 resistance gene were initiated. Treatment of cells with various elicitors, except AVR9, induced an oxidative burst, ion fluxes, and expression of defense-related genes. Agrobacterium tumefaciens-mediated transformation of Cf9 tomato leaf discs with Avr9-containing constructs resulted efficiently in transgenic callus formation. Although transgenic callus tissue showed normal regeneration capacity, transgenic plants expressing both the Cf-9 and the Avr9 genes were never obtained. Transgenic F1 seedlings that were generated from crosses between tomato plants expressing the Avr9 gene and wild-type Cf9 plants died within a few weeks. However, callus cultures that were initiated on cotyledons from these seedlings could be maintained for at least 3 months and developed similarly to callus cultures that contained only the Cf-9 or the Avr9 gene. It is concluded, therefore, that induction of defense responses in Cf9 tomato cells by the AVR9 elicitor is developmentally regulated and is absent in callus tissue and cell-suspension cultures, which consists of undifferentiated cells. These results are significant for the use of suspension-cultured cells to investigate signal transduction cascades.

Journal Article↗

Malignant splenic lymphoma: sonographic patterns, diagnosis and follow-up.

UNLABELLED: Six hundred and eighty patients with malignant lymphoma were studied by abdominal sonography during 1983 and 1993 at our institution. Abnormal splenic texture was noted in 101 patients (14,8%). Involvement of the spleen was confirmed histologically (n = 8), by sonographic follow-up (n = 82), and on the basis of the clinical course in the remaining patients. Of the 101 patients with splenic involvement, 34 had Hodgkin's disease, 38 had a low-grade non-Hodgkin's lymphoma and 29 a high-grade non-Hodgkin's lymphoma. Four different sonographic patterns were observed: (1) Diffuse involvement in 37 patients (pts) (36.6%). (2) Focal small nodular lesions in 39 pts (38.6%). (3) Focal large nodular lesions in 23 pts (22,7%). (4) 'Bulky, disease' in two pts (1.9%). All of the high-grade lymphomas showed either large nodular (15/29) or small nodular (14/29) lesions. The diffuse or small nodular pattern was seen predominantly in low-grade lymphomas (35/38) and in Hodgkin's disease (31/34). CONCLUSION: A number of different patterns of splenic involvement in lymphoma can be demonstrated by ultrasound. Splenic sonographic patterns can be linked to histological lymphoma entities.

Adolescent↗

Chronic eosinophilic leukaemia (CEL): a distinct myeloproliferative disease.

Chronic eosinophilic leukaemia has not yet been clearly defined, mainly due to the fact that it has not been conclusively shown as a monoclonal disease which should be separated from chronic myelogenous leukaemia, acute myelogenous leukaemia with eosinophilia (AML, FAB M4Eo), and the idiopathic hypereosinophilic syndrome. We report a patient with a white blood cell count of 17.6 x 10(9)/l with 74% eosinophils, normal platelet count and haemoglobin. No blasts were seen in the peripheral blood and the percentage of blasts in the bone marrow was < 3%. A diagnosis of chronic eosinophilic leukaemia was made. Chromosome analysis of a bone marrow aspirate disclosed a trisomy 15 together with loss of the Y chromosome. Moreover, FISH analysis on May-Grünwald-Giemsa-stained peripheral blood smears demonstrated trisomy 15 in the eosinophils. 3 months after initial diagnosis the patient went into blast crisis and died. The blast cells exhibited trisomy 15 and loss of the Y chromosome in a complex, aberrant karyotype. In conclusion, the case shows that chronic eosinophilic leukaemia is a monoclonal, myeloproliferative disease with eosinophils as part of the malignant clone. Clinically, chronic eosinophilic leukaemia can be separated into a chronic phase and a blast crisis.

Blast Crisis↗

Sonographic patterns in extranodal abdominal lymphomas.

Between 1980 and 1993, 680 patients with non-Hodgkin's lymphomas (NHL) and Hodgkin's disease (HD) were studied by ultrasonography. In 210 patients a total of 254 extranodular abdominal lymphoma infiltrates were diagnosed. Infiltrates were confirmed histologically in 118 patients and through the clinical course and follow-up studies in 92 patients. Lymphoma infiltrates were seen most frequently in the spleen (n = 101), the gastrointestinal tract (n = 70), the liver (n = 47), the kidneys (n = 17) and other organs (n = 19). The sonographic features of lymphomatous infiltrates in different extranodal sites are described, and possible correlations between lymphoma subtypes and sonographic texture characteristics are investigated. Different infiltration patterns of lymphoma subtypes could be identified in liver and spleen. High-grade NHLs most frequently showed large-nodular lesions, whereas low-grade NHLs and HD showed a tendency towards small-nodular or diffuse lesions. The role of ultrasonography in the clinical management of lymphoma patients is discussed.

Abdominal Neoplasms↗

Successful treatment of osteoporosis in systemic mastocytosis with interferon alpha-2b.

Osteoporosis is frequently seen in systemic mastocytosis. Although diphosphonate therapy has been shown to be transiently effective, therapy options for this form of osteopenia are very limited. We have treated three patients with systemic mastocytosis and osteopenia successfully with interferon alpha-2b. Two patients had urticaria pigmentosa and two severe back pain due to vertebral compression fractures. All patients received a daily interferon dose of 3 x 5 mio units/week s.c. for a period of 6 months. Therapy was well tolerated, and back pain resolved in both patients. A marked decrease of mast cell numbers in the bone marrow and a significant increase of bone mineralization and bone density was observed in all patients. Our data suggest that alpha interferon may be a new treatment option for osteopenia in systemic mastocytosis.

Adult↗

Storage of noncryopreserved periphered blood stem cells for transplantation.

Mobilized peripheral blood stem cells (PBSC) were collected in autologous plasma and acid-citrate-dextrose formula A (ACD-A) by leukaphereses using the CS3000 cell separator (Baxter) and stored at 4 degrees C in a refrigerator for 8 days. We have looked at the viability of the nucleated cells with the trypan blue test and the proliferation and differentiation capacity using a standardized progenitor cell cloning assay. The changes in viability, granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst-forming units (BFU-E), and mixed-lineage colony-forming units (CFU-GEMM) were determined daily during the storage period. Viability was 90.8% (SD 8%) at day 0 and declined to a mean of 69.5% (SD 15.5%) at day 8. CFU-GM decreased to 47% (SD 28.7%), CFU-GEMM to 48% (SD 42.2%), and BFU-E to 40.1% (SD 18.4%) after 6 days. After 5 days of storage the mean viability was 79.7% (SD 17.8%), whereas the mean CFU-GM were 65.3% (SD 28.4%) the mean CFU-GEMM were 61.8% (SD 30.4%) and the mean BFU-E were 55.1% (SD 18.2%). At day 4 viability was still 82.5% (SD 17.0%), recovery of CFU-GM was 78.5% (SD 28.8%), recovery of CFU-GEMM was 70.7% (SD 40.4%) and recovery of BFU-E was 65.0% (SD 17.5%). These data show, that PBSC can be stored safely over at least 5 days at 4 degrees C while the patient receives high-dose chemotherapy.

Blood Component Removal↗

[Ultrasound manifestations of abdominal lymphomas. An overview].

Abdominal sonography is now the most frequently used screening method for the detection of abdominal lymph node enlargement. For proper classification, size, localisation and infiltration pattern must be known. The definitive determination whether lymph nodes are benign or malignant cannot be made by the size of the lesion alone. The localisation (parietal/visceral) of enlarged lymph nodes has been shown to be of significance in the staging of abdominal carcinomas. Different infiltration patterns (diffuse small nodular, focal small nodular, focal large nodular, bulky formations) show the broad spectrum of abdominal lymphomas detected by ultrasound. Knowledge of these different infiltration patterns together with clinical information often helps to discriminate between lymph node enlargement caused by inflammation, metastasis, or malignant lymphoma. The definitive diagnosis is made via laparotomy, ultrasound guided biopsy or sonographic follow-up studies.

Abdominal Neoplasms↗