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Biomedical subjects

E Ruud

Publications and source records attributed to E Ruud.

At least 19 recordsLinked to original sources

Successful thrombolysis by prolonged low-dose alteplase in catheter-directed infusion.

UNLABELLED: Catheter-directed thrombolysis is a sophisticated method in the treatment of thromboembolism with maximum effect on the thrombus and minimal systemic effect. The consequences are enhanced local thrombolysis and a reduction in general bleeding tendency, compared with systemic thrombolysis. At our institution, two children had successful thrombolysis by prolonged continuous catheter-directed low-dose alteplase. The first patient, a boy with Fontan physiology, was successfully treated for a massive pulmonary thromboembolism by catheter-directed very low-dose alteplase for five days. The second patient, who suffered from relapsing nephrotic syndrome, achieved satisfactory thrombolysis of an arterial leg thrombosis after four days of continuous catheter-directed low-dose alteplase. CONCLUSION: Although catheter-directed thrombolysis seems to be a valuable method in thrombolytic therapy, there is a lack of evidence-based recommendations concerning dosage, effect of bolus, simultaneous anticoagulation and duration of treatment for children.

Catheterization, Peripheral↗

Unexpected medical coincidences require systematic and careful strategies: an example.

In a cohort of 14 children with identical cardiac xenografts, two boys developed acute myeloid leukaemia 11 and 16 months respectively after the operation. A dedicated working group designed a scheme intending to take care of all aspects of the situation. This article focuses on preferred strategies towards patients, relatives, government, and the media. We did not find any substantial evidence supporting the association between bovine xenografts and two cases of acute myeloid leukaemia.

Animals↗

Report of the Tumor Evaluation Committee workshops at ISHAGE 2001.

Multiple factors impact polymerase chain reaction (PCR) detection of tumor cells ranging from the fundamental, such as selection of targets for amplification, to the practical, including the timing of sample processing, granulocyte contamination and anticoagulant used. Much more work, including standardization studies, remains to be performed. Tumor enrichment can be achieved either by positive selection, generally by use of antibodies or by depletion of (CD45(+)) hematopoietic cells. Both approaches work and each has advantages and disadvantages. Enriched tumor cells can be further analyzed for expression of prognostic markers. A future area of emphasis should be to establish a dialogue between practitioners of tumor detection and developers of new therapies who are in search of surrogate markers of outcomes.

Biomarkers, Tumor↗

Microcephalus, medulloblastoma and excessive toxicity from chemotherapy: an unusual presentation of Fanconi anaemia.

UNLABELLED: Fanconi anaemia is a genetically and phenotypically heterogeneous disorder with different forms of clinical presentation. In this case the patient had suffered from microcephalus and delayed motor development from birth, but extensive investigation did not disclose any aetiology. At 3.5 y she developed a cerebellar medulloblastoma which was treated with surgery and chemotherapy. Following chemotherapy with alkylating agents she suffered from severe bone marrow aplasia which caused life-threatening infections, feeding problems and impaired kidney function. Fanconi anaemia was suspected, but it took 2 mo before the chromosome fragility test came out positive. From the moment diagnosis of Fanconi anaemia was made, no further active treatment was given. The patient's condition improved for some time, but she relapsed and died exactly 1 y after the first diagnosis of brain tumour. CONCLUSION: Fanconi anaemia must always be suspected in patients who experience excessive toxicity from chemotherapy regardless of the type of malignancy and congenital malformations.

Antineoplastic Combined Chemotherapy Protocols↗

Detection of disseminated tumor cells in peripheral blood of colorectal cancer patients.

All cancer staging systems seek to identify clinical and pathological features that can predict outcome or guide therapy. In particular, a non-invasive method for the early detection of disseminating disease would be of great interest. We investigated the use of cytokeratin genes expression to detect blood metastases from colorectal tumors. Epithelial tumor cells were isolated from whole blood using the monoclonal antibody (MAb) BerEP4 and magnetic beads, and detected by reverse transcription-polymerase chain reaction using oligonucleotides derived from the cDNA sequences of cytokeratins 8, 19 and 20. The sensitivity of this assay was determined by spiking SW620 colon carcinoma cells in normal blood. Using cytokeratin 19 expression we were able to detect 1 epithelial tumor cell in 1 ml of whole blood. The clinical applicability of this technique was explored by evaluating patients with a colorectal carcinoma. Epithelial cells were detected in the blood of 12 out of 23 patients, 2 (20%) of 10 with Astler-Coller stage A or B, and 10 (77%) of 13 with stage C or D cancer. In conclusion, this test is a non-invasive, sensitive, and specific assay for detecting circulating epithelial cells in blood. It may be useful for the early diagnosis of disseminating disease, to determine whether the presence of micrometastatic cells at the time of surgery is correlated with an early relapse and for monitoring adjuvant therapeutic trials.

Adult↗

[Phimosis can be treated with local steroids].

The effectiveness of topical steroid application in relieving phimosis was studied in 41 boys treated with a potent steroid ointment. 35 patients showed improvement initially but in 12 of them the phimosis recurred completely and in seven of them partly. There was significantly less recurrence in the patients who improved within one month. Most of the families were satisfied with the treatment. We recommend topical steroids as first treatment of choice for phimosis, when treatment is necessary.

Administration, Topical↗

Heterogeneity of degradation of B-cell endocytosed monoclonal antibodies reacting with different sIgM epitopes.

The degradation of a panel of monoclonal antibodies (MoAb) bound to surface IgM (sIgM) was studied in three human Burkitt's lymphoma cell lines. The panel included MoAb that recognize several distinct epitopes associated with the F(c mu)5 domain, the c mu 2 domain and kappa or lambda light chains. The amount of degraded MoAb and the rate of their degradation varied considerably between the various antibodies. Properties of MoAb such as avidity or ability to cross-link sIgM did not significantly influence their degradation. The most consistent correlation between rate of degradation and MoAb used was the location of the epitope recognized by the individual MoAb. Thus, 7 out of 8 anti-light chain MoAb were degraded at a higher rate than 5 out of 5 anti-F(c mu)5 MoAb. One anti-c mu 2 MoAb was degraded at a rate similar to the majority of anti-light chain MoAb. The intracellular transport of an anti-kappa light chain MoAb and an anti-F(c mu)5 MoAb was studied in detail by subcellular fractionation in sucrose gradients. We found that the anti-kappa light chain MoAb was transported more rapidly to lysosomes than the anti-F(c mu)5 MoAb, showing that they were sorted differently intracellularly.

Animals↗

Degradation of a monoclonal anti-mu chain antibody in a human surface IgM-positive B cell line starts in prelysosomal vesicle.

The surface IgM-mediated endocytosis and intracellular transport of an anti-F(c mu)5 mAb was studied by using subcellular fractionation in sucrose gradients. The results of such experiments showed that antibody was initially endocytosed in vesicles of low density, and later transferred to a presumably lysosomal compartment of higher density. SDS-PAGE analysis of gradient fractions showed that high Mr degradation fragments of the endocytosed antibody were formed in the low density vesicles before terminal degradation could be recorded. The partial degradation of the antibody was not blocked by low temperature or enzyme inhibitors, such as leupeptin and benzyloxycarbonyl-phenylalanylalanine-diazomyethyl-ketone, all of which severely retarded terminal degradation. The data also suggested that the recycling of partially degraded antibody to the cell surface employed a pool of such low density prelysosomal vesicles.

Animals↗

Cyclic AMP has the ability to influence multiple events during B cell stimulation.

Negative regulators of cellular proliferation are important in maintaining a balanced growth control. In this study we have examined the effects of the diterpene forskolin on various parameters of B cell activation. Forskolin is known to elevate intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels and thereby to influence B cell stimulation. We found that forskolin exerted an inhibitory effect on early as well as late events during stimulation of resting normal human B cells. Cells were activated either by antibodies to surface immunoglobulins (anti-mu), by the monoclonal antibody 1F5 reactive with the CD20 antigen or by 12-O-tetradecanoylphorbol 13-acetate. While anti-mu stimulation induces increased phosphatidylinositol (PI) turnover and [Ca2+]i fluxes, the latter two reagents confer an activation of B cells independent of the PI/Ca2+ pathway. We found a clear inhibitory effect of forskolin on the anti-mu-induced PI turnover and [Ca2+]i fluxes as well as on later parameters of cell activation. There was also a clear inhibition of G1 entry and DNA synthesis when PI/Ca2+-independent activation was employed, indicating that cAMP interferes with B lymphocyte stimulation in several ways. Importantly, forskolin maintained its inhibitory effect when added late after anti-mu stimulation, implying an effect also at multiple stages of activation. When examining the inhibitory effect of forskolin on neoplastic B cells, we found essentially no differences from the responses in normal cells.

Antibodies, Monoclonal↗

Potential multiple functions of the v-myc oncogene within a single cell clone of OK10 retrovirus-transformed quail fibroblasts.

Propagation of in vitro transformed OK10 QDP 9c cells, cloned in soft agar, results in selective amplification of the OK10 pro-viral genome to yield a 12-fold increase in v-myc oncogene expression. In addition, increased v-myc oncogene dosage correlates with an increase of the proliferative potential of already transformed cells and relieves dependence on high serum concentrations for optimal cell growth. The increased rate of cell proliferation is reflected by a much more rapid progression through all parts of the cell cycle. These results suggest that the attainment of transformed status on one hand and progressive increase in growth factor independence for optimal cell proliferation on the other hand, may be initiated by different myc oncogene dosages within the OK10 QDP 9c cell clone.

Animals↗

Attention deficit disorders: a study of peptide-containing urinary complexes.

In several behavioral disorders, we have observed that abnormal amounts of peptides and protein-associated peptide complexes are excreted in the urine. The gel filtration patterns of these excreted substances have some specificity for the different disorders. The urinary excretion of peptide-containing complexes was studied in 91 boys and 13 girls (mean age 9.4 years, range 1-23) with the clinical diagnosis of attention deficit disorder (ADD), with or without hyperactivity. The gel filtration of urine precipitate showed patterns in all patients that were different from those seen in 36 normal controls. Sixty-four patients had increased benzoic acid-glycoprotein-peptide complexes in the late peaks. The symptoms of all these patients fit the criteria for diagnosis of attention deficit disorder with hyperactivity (ADDH). Thirty-five patients showed reduced amounts of uric acid complexes in the late peaks. Clinically, this group, with the exception of three patients, fit the criteria for diagnosis of attention deficit disorder without hyperactivity. Five patients showed reduced amounts of all urinary complexes; four of these were hyperactive. Moderate exercise in control children did not change the urinary pattern. One urinary peptide fraction from hyperactive patients, purified to homogeneity, increased the uptake of 14C[5-HT] in platelets. Strict clinical, neuropsychological, and psychophysiological selection of the patients reduced the heterogeneity of the patterns. Although more studies are needed, the findings seem promising for the possibility of developing biochemical tests that may be helpful diagnostically.

Adolescent↗