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B Pedersen

Publications and source records attributed to B Pedersen.

At least 37 records · Page 2Linked to original sources

Relation of blast cell survival and proliferation to chemotherapy resistance in AML.

We have investigated the in vitro blast cell survival (viability) and drug resistance to cytosine arabinoside (Ara-C), daunorubicin (Dau), mitoxantrone (Mitox) and aclarubicin (Acla) of fresh leukaemic blast cells from 80 patients with newly diagnosed acute myeloid leukaemia (AML) employing the semiautomated colourimetric MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide)-assay. In 15 cases we concurrently investigated the relation between in vitro blast cell survival (MTT assay) and blast cell proliferation (3H-thymidine incorporation) in the presence and absence of myeloid growth factors (GFs) G-CSF, GM-CSF and IL-3 (individually and in combination). A highly significant correlation was found between blast cell survival and blast cell proliferation (r = 0.87, P < 1 x 10(-4). Furthermore, in 40 evaluable adult patients who completed intravenous induction chemotherapy and were evaluable for response to chemotherapy we found a positive correlation between in vitro blast survival (MTT assay) and response to chemotherapy with high blast survival being associated with poor response to chemotherapy (P = 0.05). Moreover, in a multivariate analysis, high blast cell survival was significantly associated with high CD13 expression and monocytic phenotype (P = 0.0003 and P = 0.02, respectively). Furthermore, we found an inverse relationship between the baseline proliferation of the blasts and the magnitude of response to the GFs (P < 0.02), indicating that cells with low baseline proliferation were more readily stimulated by growth factors. Finally, we found a significant correlation between leukaemic cell survival and cellular drug resistance towards Dau (P = 0.001) and Mitox (P = 0.03), but not towards Ara-C (P = 0.68) and Acla (P = 0.13). We conclude that high in vitro leukaemic cell survival is associated with drug resistance in vivo and in vitro, and furthermore is correlated with high blast cell proliferation and some adverse prognostic factors previously identified in AML.

Aclarubicin

The effect of iron chelation on haemopoiesis in MDS patients with transfusional iron overload.

Long-term follow-up data are presented on changes in peripheral blood counts and Hb requirements of 11 patients with myelodysplastic syndromes (MDS) during iron chelation treatment with desferrioxamine for up to 60 months. The erythroid marrow activity was indirectly evaluated by repeated determinations of the serum transferrin receptor concentration. The efficacy of iron chelation was evaluated by repeated quantitative determination of the liver iron concentration by magnetic resonance imaging. Reduction in the Hb requirement ( > or = 50%) was seen in 7/11 (64%) patients. Five patients (46%) became blood transfusion independent. Platelet counts increased in 7/11 (64%) patients and the neutrophil counts in 7/9 (78%) evaluable patients. All patients in whom iron chelation was highly effective showed improvement of erythropoietic output accompanied by an increase in the serum transferrin receptor concentration. It is concluded that reduction in cytopenia in MDS patients may be accomplished by treatment with desferrioxamine, if the iron chelation is efficient and the patients are treated for a sufficiently long period of time. Exactly how treatment with desferrioxamine works remains a challenge for further investigation.

Adolescent

Controlled trial of lamotrigine (Lamictal) for treatment-resistant partial seizures.

The antiepileptic effect of lamotrigine (Lamictal) was assessed in a double-blind, placebo-controlled, crossover trial in 56 adult patients with refractory partial seizures. Lamotrigine or placebo was added to the patients' existing antiepileptic drugs (AEDs). The dose of lamotrigine varied from 75 to 400 mg daily. Thirty-eight patients completed the trial and 7 withdrew because of adverse experiences. There was a statistically significant reduction in seizure counts on lamotrigine compared with placebo for total seizures (30.3% reduction, 95% CI 8.4%, 47.0%), complex partial seizures (29.2% reduction, 95% CI 3.8%, 47.9%) and secondary generalised seizures (37.9%, CI 18.9%, 52.4%). The analysis of total seizure days showed a similar significant reduction during lamotrigine treatment for the same seizure categories. There was no statistically significant difference in reporting of adverse events between lamotrigine and placebo except for dizziness which was reported more frequently on lamotrigine than on placebo. There were no differences in abnormal haematological or biochemical findings between lamotrigine and placebo, and lamotrigine had no effect on plasma concentrations of concomitant AEDs.

Adolescent

Maternal HLA class II alleles predispose to pregnancy losses in Danish women with recurrent spontaneous abortions and their female relatives.

PROBLEM: If damage to the trophoblast mediated through autoimmune mechanisms is responsible for recurrent spontaneous abortions (RSA), maternal class II HLA antigens might be expected to be involved. We wanted to evaluate the impact of these antigens on pregnancy outcome in RSA women and their relatives. METHOD: HLA-DR and -DQ typing using RFLP and PCR-SSP methods was carried out in 234 Danish women with unexplained RSA and 360 controls. The HLA-DR types were correlated to outcome of the next pregnancy in 94 patients. Sisters, brothers, and wives of brothers of 146 consecutive patients were HLA typed and their pregnancy outcomes were correlated to the HLA-DR types. RESULTS: HLA-DR1/Br and -DR3 were each significantly increased in women with at least four previous pregnancy losses (both P-values < 0.05 after correction for multiple comparisons). In the prospective study, 62% of the HLA-DR1/Br and/or -DR3 positive patients miscarried the next pregnancy compared with only 29% of those negative for both allogenotypes (P = 0.025). The family studies indicated that female relatives of RSA patients had a greater risk (odds ratio = 5.0, 95% CI = 2.0-11.0) of pregnancy losses when positive for HLA-DR1/Br and/or -DR3 than those negative for the allogenotypes. CONCLUSIONS: Maternal HLA-DR allogenotypes DR1/Br and -DR3 or closely linked genes seem to predispose to pregnancy losses in RSA patients and their first degree relatives.

Abortion, Habitual

Subcutaneous administration of hyaluronan reduces the number of infectious exacerbations in patients with chronic bronchitis.

Hyaluronan (HA) is a high molecular weight glycosaminoglycan found in large amounts in the skin, joints, and other organs. Previous studies have shown that HA stimulates neutrophil functions both in vitro and in vivo. The object of this study was to test the hypothesis that HA administration subcutaneously might reduce the number of bacterial infections in humans with an increased susceptibility to such infections. For this purpose we have studied 29 patients with chronic bronchitis and recurrent acute exacerbations of their disease. The patients were randomly separated into two groups. One group had HA for 6 mo followed by 6 mo of placebo, and the other group started with placebo treatment followed by HA. The treatment periods occurred during two consecutive winter periods. HA-treated patients had significantly fewer acute exacerbations (p = 0.01) than did placebo-treated patients. Likewise the consumption of antibiotics and other signs of bacterial infections were reduced. In the crossover study the placebo-treated patients again had much higher numbers of acute exacerbations than did the HA-treated patients (p < 0.0001). It is concluded that HA reduces the number of infectious exacerbations in patients with chronic bronchitis, possibly by enhancing cellular host defense mechanisms. HA is a new endogenous substance that can be used to stimulate host defense reactions and reduce the need of antibiotics. Before being recommended for clinical use, however, our results should be confirmed by further studies.

Aged

Eosinophil and neutrophil activity in asthma in a one-year trial with inhaled budesonide. The impact of smoking.

The object of this investigation was to study the long-term effects of antiasthma treatment on blood markers of inflammation and lung function in adult asthmatic subjects. For this purpose 85 allergic and nonallergic asthmatic subjects were randomized into three groups, which were given high-dose (1,600 micrograms/d) inhaled budesonide, low-dose (400 micrograms/d) inhaled budesonide, and oral theophylline (600 mg/d), respectively, and were followed for 11 mo with testing of lung function and blood sampling for the assay in serum of eosinophil cationic protein (ECP), eosinophil protein x/eosinophil derived neurotoxin (EPX/EDN) as eosinophil markers, and myeloperoxidase (MPO) and lactoferrin (LF) as neutrophil markers. Lung functions (FEV1% predicted, and histamine PC20) and the eosinophil markers ECP and EPX/EDN were improved and reduced, respectively, by budesonide in a dose-dependent and temporally parallel fashion. Theophylline did not alter lung functions but reduced ECP and EPX/EDN after prolonged treatment. The treatment efficacy of budesonide was attributed solely to an effect on nonsmoking asthmatic subjects, since neither lung functions nor eosinophil markers changed in smokers even with high-dose budesonide. MPO but not LF was reduced after several months of treatment in all three groups, but only in nonsmokers. We conclude that ECP and EPX/EDN may be used to monitor antiinflammatory treatment in asthmatic patients, and that smoking asthmatic subjects are resistant to inhaled corticosteroids.

Adult

Clonal chromosome aberrations in myeloid leukemia after styrene exposure.

OBJECTIVES: The purpose of the study was to determine the risk of myeloid leukemia subclassified according to clonal chromosome aberrations in styrene-exposed workers. METHODS: A nested case-referent study was carried out on 19 myeloid leukemia patients, of which 12 showed clonal chromosome aberrations, and 57 referents ascertained within the Danish reinforced plastics industry and similar industries with no styrene exposure. RESULTS: A 2.5-fold increased risk for myeloid leukemia with clonal chromosome aberrations (95% confidence interval 0.2-25.0) was found among workers of companies with styrene exposure. CONCLUSIONS: The results suggest that styrene may cause leukemia through a clastogenic effect. But similar findings could also have been found if the exposure was associated with a specific subtype of leukemia prone to develop the chromosome aberrations in question. Due to the few observations and the lack of detailed exposure data, additional studies are needed to corroborate or refute the present suggestive findings.

Adult

Pig farmers have signs of bronchial inflammation and increased numbers of lymphocytes and neutrophils in BAL fluid.

The purpose of this study was to investigate whether pig farmers had inflammation of the bronchial mucosa and activation of bronchoalveolar lavage (BAL) cells. Pig farmers are exposed to high dust levels and have a prevalence of work-related respiratory symptoms. Bronchoscopy and BAL were performed in 27 young large-scale pig farmers, who had never smoked. Fifty three lifetime nonsmoking healthy students participated as controls. All farmers and controls had normal lung function (forced expiratory volume in one second (FEV1) 109 and 105% predicted respectively. Estimation of macroscopic signs of inflammation in the bronchi (erythema, oedema, secretion and friability) showed that pig farmers had significantly increased signs of inflammation. The median score was 3 (range 0-6) compared to a median score of 0 (range 0-3) in controls. More pig farmers than controls (41 versus 25%) had a positive histamine challenge (provocative dose producing a 20% fall in FEV1 (PC20) < or = 32 mg.mL-1) but the difference was not significant. The cell concentration in BAL fluid was identical in the two groups. Pig farmers had a significantly increased percentage of lymphocytes (median 7, range 1-27 versus median 2, range 0-7) and neutrophils (median 2, range 0-30 versus median 1, range 0-4) compared to controls. Spontaneous migration (19.8 versus 5.5 microns) and chemotaxis (62.6 versus 11.2 microns) was significantly increased in pig farmers compared to controls. After stimulation with zymosan and phorbol myristrate acetate (PMA), the reactive oxygen radical generation of purified alveolar macrophages was also significantly increased in pig farmers. Lifetime nonsmoking pig farmers with normal lung function have macroscopic signs of bronchial inflammation and an increased number of neutrophils in bronchoalveolar lavage. Their alveolar macrophages showed biological signs of activation. The inflammation of pig farmers bronchi may be early signs of bronchitis.

Adult

Anatomy of the 5q- deletion: different sex ratios and deleted 5q bands in MDS and AML.

Deletion of part of the long arm of chromosome 5 (5q-) is the most common structural chromosome aberration in patients with myeloid disorders. Most patients are women. Although widely varying 5q segments are deleted, the vast majority of cases share a common deleted region (5q31). Whether or not other deleted 5q regions are of clinical importance is unknown. In an attempt to throw light on this question, 439 published 5q- cases were analyzed. The female preponderance was found to be limited to refractory anemia (RA), RA with excess of blasts (RAEB) and myeloproliferative disease, all with 5q- as the only chromosome aberration. When other chromosome aberrations had developed or the diagnosis was AML, only marginal female preponderance was observed. The 5q31 was deleted in all patients with MDS and 5q- as the only aberration. In contrast, in AML and following cytogenetic progression other bands were deleted more often than 5q31. This difference, together with a different female preponderance suggests diverse pathogenetic mechanisms in MDS and AML. Furthermore, the bands 5q13-5q21 were found to be of importance for clinical progression from RA to RAEB, and 5q22-5q33 of importance for development of AML and cytogenetic progression. In conclusion, the 5q bands deleted affect both clinical and cytogenetic progression.

Acute Disease

Assessment of the allergic reaction in seasonal rhinitis: acoustic rhinometry is a sensitive and objective method.

BACKGROUND: Seasonal allergic rhinitis constitutes an excellent in vivo model of an allergic mucosal inflammatory reaction. This offers the opportunity of studying the fundamentals of allergic inflammation in addition to improvement of knowledge on the basal pathophysiological mechanisms of the disease. So far, monitoring methods of disease activity and treatment efficacy have mainly been based upon subjective assessments, illustrating the impact of introducing reliable objective methods. OBJECTIVE: To investigate the allergic inflammatory reaction of seasonal rhinitis through different objective methods and evaluate these as indicators of disease activity and treatment efficacy. METHODS: Functional parameters, i.e. acoustic rhinometry and nasal metacholine challenge, and biological markers, i.e. blood eosinophil count, eosinophil cationic protein in serum (s-ECP) and nasal lavage fluid (n-ECP), were assessed before and at peak pollen season in 27 patients with grass pollen induced rhinitis. Patients were randomized to either nasal corticosteroid or placebo treatment and recorded nasal symptom scores. RESULTS: Acoustic rhinometry revealed a significant difference in favour of steroid treatment (P < 0.05) comparing nasal volumes before and during season. This difference primarily relied upon a decrease in the placebo group (P = 0.05). A reduction from baseline of s-ECP in the steroid group (P < 0.01) was obtained. N-ECP demonstrated a difference between treatment groups, although not significant. Symptom scores increased in all patients during the pollen season, although this was only significant in the placebo treated patients (P < 0.01). The remaining methods applied did not demonstrate further differences, either within or between treatment groups. CONCLUSION: Our results demonstrate acoustic rhinometry to be a sensitive and objective method of assessment of nasal obstruction. Furthermore, acoustic rhinometry and s-ECP reflect the impact of nasal steroid therapy on seasonal allergic rhinitis.

Acoustics

Partial triplication (7q) in a child with acute lymphoblastic leukemia demonstrated with conventional cytogenetics, PRINS, and chromosome painting.

In this report we describe a partial triplication (7q) and other structural aberrations found in a child with acute lymphoblastic leukemia (ALL), and we demonstrate the importance of PRimed IN Situ labeling (PRINS) and chromosome painting as a support to banding analysis for the clarification of complex structural chromosome rearrangements. Initially, the der(7) was interpreted as der(7)t(1;7;7). However, PRINS and chromosomes painting showed that der(7) consisted entirely of chromosome 7 material. Further, a derivative chromosome interpreted by banding analysis as a der(17)t(?1;17) was shown to be der(17)t(13;17) by the newly developed PRINS painting technique.

Child

[Attitude and considerations of sperm donors in relation to insemination].

The object of the study was to examine sperm donors' motivations and emotional reactions to the role as donors and to measure their willingness to provide information about themselves to recipients and offspring. It was designed as a prospective trial in which 26 subjects who were actively functioning as sperm donors at our fertility clinic at the time of investigation were asked to fill in a questionnaire and return it anonymously and voluntarily. Eight percent of the donors stated purely altruistic motivation, 32% purely financial and 60% a combination of both. The acceptance rate for providing non-identifying, phenotypic, descriptive information to recipients is 76%, for providing medical information it is 60% and the provision of psychosocial information is accepted by 28% to 40% depending on the item. Twenty percent of donors are willing to continue donation if the present rules of anonymity are revoked, 20% were undecided. In conclusion, most donors do not seem to feel any close relationship to donor offspring and at least 60% found anonymity to be essential for their continued functioning as donors.

Adult

The reliability of preconization diagnostic evaluation in patients with cervical intraepithelial neoplasia and microinvasive carcinoma.

The accuracy of preconization cytology and histology was evaluated in 536 patients undergoing combination laser conization. Exact agreement between cytology and cone diagnosis was observed in 41.8% of the patients. The lowest agreement, 13.6% was demonstrated in cytologic cervical intraepithelial neoplasia (CIN) I, the highest in cytologic CIN III, 64.3%. Concerning microinvasive disease, the positive predictive value of cytology was only 27.3%; the negative predictive value 94.6%. When cytology showed CIN II or worse, the cone biopsy showed CIN or invasive disease in 92.8%. Exact agreement between preconization histology and the cone biopsy was found in 59.5%. Highest agreement was observed in CIN III lesions, 67.1%, and the lowest agreement in CIN II lesions, 42.7%. When preconization showed CIN II, a higher grade of lesion was found in the cone biopsy in 29.1%. Cone biopsy revealed invasive disease in 38 cases. In 24 cases, invasive disease was not demonstrated prior to conization, corresponding totally to 4.7% of patients not suspected to have invasive disease prior to conization. Regarding invasive disease, the sensitivity of preconization histology was 36.8%, the positive predictive value 58.3%, and the negative predictive value 95.3%. Kappa statistics demonstrated rather low agreement between cone diagnoses and preconization diagnoses. These results confirm the potential risk of overlooking invasive disease by conventional preconization evaluation and demonstrate the need for excisional methods in the management of cervical intraepithelial neoplasia to provide a sufficient specimen for diagnostic purposes. Combined with the therapeutic results, combination laser conization was a reliable diagnostic and therapeutic method in the management of patients with CIN and microinvasive cancer of the cervix.

Conization

Myelodysplastic syndrome in a child with constitutional trisomy 8 mosaicism and normal phenotype.

Trisomy 8 is a frequently acquired cytogenetic abnormality in myeloid malignancies, but may also represent a constitutional chromosome abnormality with a wide phenotypic variation. We report a case of myelodysplastic syndrome (MDS) that developed in a child with trisomy 8 mosaicism and normal phenotype. Bone marrow (BM) cells all showed trisomy 8 with additional clonal abnormalities in most cells. Based on the present case and a review of previously published cases of myeloid malignancies in patients with trisomy 8 mosaicism, it appears likely that the malignant cells developed from the trisomic cell population, suggesting that constitutional trisomy 8 may be a predisposing condition to myeloid malignancies. Trisomy 8 in malignant cells is usually considered an acquired abnormality, but this implies a risk of ignoring a constitutional trisomy 8 mosaicism. Examination for constitutional trisomy 8, despite a normal phenotype, may therefore be warranted in hematologic malignancies with trisomy 8 of BM cells to evaluate further the possible association and to preclude erroneous use of trisomy 8 as a tumor marker.

Child

Translocation (1;16) identified by chromosome painting, and PRimed IN Situ-labeling (PRINS). Report of two cases and review of the cytogenetic literature.

We used the molecular cytogenetic in situ techniques chromosome painting and PRimed IN Situ labeling (PRINS) to elaborate the cytogenetic observations in two cases of the rare aberration der(16)t(1;16), which occurs in a wide variation of hematologic and nonhematologic malignancies [1-3]. Review of the literature showed that, in contrast to the chromosome 1 breakpoint, the breakpoint on chromosome 16 is associated with diagnosis as well as patient age.

Adult

Foot deformity and the length of the triceps surae in Danish children between 3 and 17 years old.

We report the results of examination in 1991 of 759 children and adolescents between 3 and 17 years old, comprising 98% of pupils in different age groups from seven schools and ten kindergartens in Funen (Denmark). The triceps surae was considered to be short if the foot held with the talus in neutral position relative to the calcaneus could only be dorsiflexed to a right angle. The proportion of children with shortening of one or both triceps surae rose from 24% to 62% between the ages of 3 and 17 years with no difference between the sexes. In 13% of adolescents, one or both feet failed to reach a right angle by > or = 5 degrees. Footprints made in 1,520 feet showed that the proportion of feet with a high arch increased from 2% to 7%; there was a smaller number of such feet with a short triceps surae than in feet with a normal arch. The proportion of feet with a flat arch declined from 42% to 6% in spite of a strong relationship with a short triceps surae. In the oldest age group, all the flat feet had a short triceps surae, which is probably one of the reasons for the persistence of the deformity.

Adolescent

Once daily fluticasone propionate aqueous nasal spray controls symptoms of most patients with seasonal allergic rhinitis.

This multicentre, randomized, double-blind, parallel-group study was designed to compare the efficacy and tolerability of fluticasone propionate aqueous nasal spray 200 micrograms once daily (FPANS 200 micrograms od) with FPANS 200 micrograms twice daily (bd) in patients whose seasonal rhinitis symptoms were not completely controlled with FPANS 200 micrograms od. A total of 549 patients initially received FPANS 200 micrograms od during the open-treatment phase of the study. After 2 weeks, 65% of patients had their symptoms well controlled by FPANS 200 micrograms od and continued with this treatment for a further 2 weeks. The remainder received either FPANS 200 micrograms od or FPANS 200 micrograms bd for a further 2 weeks. Efficacy was evaluated by the analysis of symptom-free days. In the uncontrolled group, there was a significant increase in the percentage of symptom-free days in the FPANS 200 micrograms bd group over the FPANS 200 micrograms od group for nasal blockage on waking (P < 0.05) and nasal blockage during the day (P < 0.05). Similar trends were observed for sneezing, rhinorrhoea, nasal itching, and eye symptoms. There was a significant increase in the percentage of days with a symptom score of less than 2 in FPANS 200 micrograms bd group for nasal blockage during the day (P < 0.05). Adverse events were similar in nature and frequency in each treatment group. It is concluded that in the majority of patients symptoms of seasonal rhinitis are well controlled by FPANS 200 micrograms od. In the minority of patients whose symptoms are not adequately controlled by a once daily dose, FPANS 200 micrograms bd provides additional relief, particularly from nasal blockage.

Administration, Intranasal