Biomedical subjects

B Swolin

Publications and source records attributed to B Swolin.

At least 37 records · Page 2Linked to original sources

PubMed1995

Bone marrow progenitor cell growth and karyotype changes in healthy 88-year-old subjects.

Previous studies have indicated a decline in bone marrow progenitor cell function in subjects aged 75-82 years, possibly causing lower Hb concentrations. We studied the bone marrow with in vitro colony assays and cytogenetic analysis in 24 apparently healthy 88-year-olds with Hb concentrations ranging from moderate anaemia to normal levels. Twenty-two healthy younger subjects, aged 21-57 years, were used as a control group. The 88-year-olds showed significantly lower numbers of myeloid bone marrow progenitors than the controls, and the elderly men had lower numbers of both erythroid and myeloid progenitors than the elderly women. There were no in vitro growth differences between elderly subjects with "low" or "normal" Hb concentrations. Ten out of 14 men had bone marrow cells with a missing Y-chromosome, which did not seem to have any relationship to the erythroid function. No morphological or other cytogenetic indications of a clonal progenitor cell disorder were found. A more rapid decline in Hb concentrations in healthy elderly men as compared to elderly women might be explained by differences in bone marrow progenitor cell function. However, progenitor cell abnormalities do not seem to explain differences in Hb concentrations within groups of apparently healthy men and women of advanced age.

Adult↗

PubMed1994

Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities.

Platelet-derived growth factor (PDGF) affects the growth, migration, and function in vitro of mesenchymal cells, but little is known about its normal physiological functions in vivo. We show here that mice deficient for PDGF B die perinatally and display several anatomical and histological abnormalities. Kidney glomerular tufts do not form, apparently because of absence of mesangial cells. Instead, a single or a few distended capillary loops fill the glomerular space. The heart and some large arteries dilate in late-stage embryos. Most PDGF B mutant embryos develop fatal hemorrhages just prior to birth. Their hematological status includes erythroblastosis, macrocytic anemia, and thrombocytopenia. On the basis of these findings, we conclude that PDGF B has crucial roles in vivo in establishing certain renal and circulatory functions.

Anemia↗

PubMed1994

Acute leukaemia after hydroxyurea therapy in polycythaemia vera and allied disorders: prospective study of efficacy and leukaemogenicity with therapeutic implications.

Fifty consecutive patients, 30 of whom had polycythaemia vera (PV), 10 essential thrombocythaemia (ET), and 10 myelofibrosis (MF), entered a long-term prospective study of hydroxyurea (HU) therapy. The indication for treatment was mainly thrombocytosis or symptomatic splenomegaly. Control of erythrocytosis and thrombocytosis was achieved in 70% of the patients. Continuous maintenance treatment was required. In 15% of responding patients with thrombocytosis, unexpected rises of the platelet count occurred during maintenance therapy. Severe thrombo-embolic events occurred in 6 patients. The size of the spleen decreased in all patients who did not develop thrombocytopenia and could absorb adequate HU doses. Acute leukaemia (AL) was diagnosed in 9 patients and a myelodysplastic syndrome in one. Seven of them had been treated with HU alone. Among the patients with PV and ET, 6 developed AL and 4 of them were treated with HU alone (3 PV and 1 ET), giving an incidence of 10.5%. In previously untreated patients with initially normal karyotypes (n = 19), chromosome abnormalities developed during HU therapy in 7 (37%). Our results indicate that HU should be regarded as leukaemogenic, at least when used for treatment of PV and allied diseases. Since myelosuppressive treatment of PV does not prolong survival, the use of HU should be restricted to patients in whom the treatment indication outweights the risk of leukaemia induction.

Acute Disease↗

PubMed1994

A follow-up study of bone marrow chromosomes and in vitro colony growth in patients with mastocytosis.

Proliferation of mast cells can give rise to many clinical manifestations in patients, and an association with hematological disorders has been pointed out. The study was initiated to determine whether patients with mastocytosis show a clinical progression in relation to bone marrow cell parameters analyzed. During a median follow-up period of 5.5 years, 10 patients with mastocytosis were re-examined with regard to clinical symptoms, urine histamine metabolites (U-MeImAA), bone marrow cells examined with chromosome analyses, and in vitro stem cell growth for CFU-GM. Seven patients showed a clinical progression with increase of either symptoms, bone marrow infiltrates of mast cells or U-MeImAA. One patient with a myeloproliferative bone marrow morphology had a malignant course. Four of the 7 patients showed an increased colony growth, while 3 showed a decreased growth, in the second examination compared with the first examination. One patient had a persistent clone with the chromosome aberration 9p+. A variable pattern was observed in the other patients, in resemblance with findings in chronic myeloproliferative disorders. Our conclusion is that mastocytosis belongs to the myeloproliferative disorders.

Adult↗

PubMed1993

Variable growth in vitro of chromosomally different stem cells in myelodysplastic syndromes.

Ten patients with myelodysplastic syndromes were investigated using in vitro colony assay of bone marrow cells and chromosome analysis of single colonies. The result was compared with conventional cytogenetic analysis of bone marrow cells. The chromosome abnormalities included were 5q-, +8, -7, 11q-, -Y and one complex karyotype. Erythroid colony formation was reduced in eight patients, while the number of granulocyte-macrophage colony-forming units was normal or increased. Cytogenetic examination of single colonies showed that both chromosomally normal and abnormal stem cells had colony forming ability. The proportion of cytogenetically abnormal colonies varied between 25 and 100% of analysed colonies. No further clones than those found in direct cytogenetic analysis were revealed after in vitro growth. One patient with a 5q- abnormality and one patient with a -7 abnormality showed a significantly lower proportion of cytogenetically abnormal colonies than the proportion of abnormal cells in the direct bone marrow chromosome preparation. One patient with a +8 abnormality showed a growth advantage of the +8 clone in comparison with the chromosomally normal clones, but this was not statistically significant. In two patients a chromosomally changed stem cell gave rise to both erythroid and myeloid colonies. The FAB-class did not seem to influence the growth of either chromosomally normal or abnormal colonies.

Aged↗

PubMed1993

Prevalence of iron deficiency in Swedish adolescents.

The prevalence of iron deficiency was determined in Göteborg, Sweden, in a sample of 15- to 16-y-old girls (n = 220) and boys (n = 207) using serum ferritin (SF). In a recent study in women on the relationship between SF and stainable bone marrow iron, it was established that at a cutoff value for SF of < 16 micrograms/L in 75% of women with no iron stores SF concentration was below this value (sensitivity 75%), whereas in 98% of iron-replete women it was above this cutoff value (specificity 98%). The present study showed that in 40% of the girls and 15% of the boys SF was below this cutoff value, indicating iron deficiency. Low SF concentration was associated with significant decreases in transferrin saturation, Hb concentration, mean corpuscular Hb, and mean corpuscular volume. The results from this cross-sectional study showed that, with decreasing SF, the decrease of values for these parameters occurred already before SF had reached the level 16 micrograms/L, suggesting that SF can be validly used as a single criterion of iron deficiency. Using the cutoff value SF < 16 micrograms/L, the figures for the prevalence of iron deficiency in adolescents in different countries were compared and found to be rather similar in Australia, Canada, the United States, and Sweden. High iron requirements combined with the present low-energy life-style leading to an insufficient supply of dietary iron may be a reasonable main explanation for the paradoxical, high prevalence of iron deficiency in adolescents in affluent societies.

Adolescent↗

PubMed1992

Rapid decline of chronic myeloid leukemic cells in long-term culture due to a defect at the leukemic stem cell level.

In this report we describe a quantitative in vitro assay for the most primitive type of leukemic precursors yet defined in patients with chronic myeloid leukemia (CML). This assay is based on the recently described "long-term culture-initiating cell" (LTC-IC) assay for primitive normal human hematopoietic cells. Such cells, when cocultured with competent fibroblast feeder layers, give rise after a minimum of 5 weeks to multiple single and multilineage clonogenic progenitors detectable in secondary semisolid assay cultures. Similar cultures initiated by seeding a highly enriched source of leukemic cells from patients onto normal feeders showed the clonogenic cell output after 5 weeks to be linearly related to the input innoculum over a wide range down to limiting numbers of input cells, thus allowing absolute frequencies of leukemic LTC-ICs to be determined using standard limiting dilution analysis techniques. Leukemic LTC-IC concentrations in CML marrow were found to be decreased, on average to less than 10% of the normal LTC-IC concentration in normal marrow, but were greatly increased (up to greater than 10(5) times) in CML blood. Assessment of the number of clonogenic cells produced per leukemic LTC-IC by comparison to normal blood or marrow LTC-IC values showed this function to be unchanged in leukemic LTC-ICs [i.e., 3.1 +/- 0.4 clonogenic cells per CML LTC-IC (mean +/- SEM, n = 6) versus 3.7 +/- 1.2 (n = 3) and 4.3 +/- 0.4 (n = 5), respectively, for normal blood and marrow LTC-ICs]. In contrast, leukemic LTC-IC maintenance in LTC proved to be highly defective by comparison to normal LTC-IC of either blood or marrow origin. Thus, when cells from primary LTC were subcultured into secondary LTC-IC assays, leukemic LTC-IC rapidly declined (greater than 30-fold) within the first 10 days of culture, whereas normal LTC-IC numbers remained unchanged during this period. These findings illustrate how self-maintenance and differentiation events in primitive human hematopoietic cells can be differentially modulated by an oncogenic process and provide a framework for further studies of their manipulation, analysis, and therapeutic exploitation.

Bone Marrow↗

PubMed1992

Dysplastic megakaryopoiesis with thrombocytopenia and chromosomal aberration.

A case of isolated thrombocytopenia with decreased platelet production and abnormal megakaryopoiesis is described. In the bone marrow, a chromosomally aberrant clone, 45,XX,-11,-18,+der (11;18)(11q13;18p11), was found. These findings indicate a myelodysplastic nature of the abnormal thrombocytopoiesis. The described case demonstrates the value of a bone marrow examination including histopathology with immunologic techniques to evaluate the megakaryopoiesis in thrombocytopenia and the interest of cytogenetic studies not only in instances with overt hematologic malignancies or complete myelodysplastic syndromes, but also when morphologic abnormalities occur in a single cell line.

Biopsy↗

PubMed1990

Cytogenetic abnormalities in acute leukemia complicating melphalan-treated multiple myeloma.

The cytogenetic findings in 11 patients with multiple myeloma in whom a myelodysplastic syndrome or an acute nonlymphocytic leukemia developed are reported. All patients were treated with oral melphalan for 2-9 years in a total dose of 0.5-4.1 g. When examined during the myelodysplastic or leukemic phase, all patients had an abnormal bone marrow karyotype, hypodiploid in nine of the 11 cases. The chromosome abnormalities were clearly nonrandom and comprised a 5q deletion in three cases, monosomy 5 in four cases, deletion 7q--in two cases, and monosomy 7 in three cases. Loss of material from the long arm of chromosomes 5, 7, or both was found in eight patients. The different chromosome abnormalities were not associated with any specific morphological or clinical features.

Aged↗

PubMed1990

Bone marrow in vitro growth and cytogenetic studies in patients with FAB-classified primary myelodysplastic syndromes.

Thirty-eight consecutive patients with a FAB-classified primary myelodysplastic syndrome (MDS) were investigated for in vitro growth of colony-forming units for granulocyte-macrophage precursors (CFU-GM) and cytogenetic analysis of bone marrow cells. Abnormal CFU-GM growth was found in 30 patients (79%), and clonal chromosome abnormalities were found in 13 patients (34%). The eight patients who showed normal CFU-GM growth were either cytogenetically normal (n = 5), or had a 5q-deletion (n = 3) as single or dominating karyotypic abnormality. Among the 30 patients with reduced or no colony growth, ten patients had a clonal chromosome abnormality. Leukemia developed in eight patients. None of them grew any CFU-GM colonies, and three of them were cytogenetically abnormal at the time of diagnosis of MDS. Analysis of the bone marrow in vitro growth for CFU-GM and the karyotype in patients with MDS emphasizes the close relationship between these disorders and manifest acute leukemia. Subgroups of MDS may be defined by a cytogenetic classification (e.g., the 5q-syndrome), and the CFU-GM growth pattern can be of value for predicting leukemic transformation.

Aged↗

PubMed1988

Recombinant interferon-alpha-2b treatment of hairy-cell leukaemia: experience with a low-dose schedule.

50 patients with hairy cell leukaemia (HCL) were treated with recombinant interferon (IFN) alpha-2b 2.0 x 10(6) IU/m2 subcutaneously three times weekly to evaluate the efficacy of low-dose IFN therapy in inducing and maintaining remission of the disease. At the time of this report 48 patients, of whom 22 were splenectomized, had been treated for at least 3 months and were considered evaluable for response. The median observation time on IFN-alpha-2b was 11 months (range 3 to 20). 4 cases with atypical disease (spongy lymphoid myelofibrosis) were also included. All patients responded to IFN. After 3 months 11/48 patients (23%) had achieved a partial remission (PR) with normalization of peripheral blood values. After 6 months 27/43 patients (63%) had achieved a favourable response; complete remission (CR) was recorded in 4 and PR in 23 patients. The proportion of patients with favourable responses (CR + PR) increased with the duration of therapy and after 12 months of therapy 23/28 (82%) patients showed CR or PR, 9 patients (32%) being in CR. Splenectomized patients disclosed a trend towards a more rapid response. It is concluded that IFN-alpha-2b is a highly effective first-line therapy for HCL.

Adult↗

PubMed1988

A prospective long-term cytogenetic study in polycythemia vera in relation to treatment and clinical course.

This paper reports the results of cytogenetic studies in a consecutive series of 64 patients with polycythemia vera, 57 of whom could be followed prospectively. The median length of the cytogenetic observation time was 93 months (range, 24 to 224 months) after diagnosis. Clonal chromosome abnormalities were observed initially in 11 patients (17%) and later during the course of the disease in another 20 patients. An abnormal karyotype was found in 71% to 80% of the patients who were examined after the development of myeloid metaplasia, myelofibrosis, or leukemia. Patients treated with myelosuppressive agents showed a significantly greater risk of chromosome abnormalities developing than did patients who had been phlebotomized. Acute leukemia developed in eight patients, all of whom had been treated with myelosuppressive agents. A chromosome abnormality preceded the leukemia in only two of the patients. The initial presence of an abnormal karyotype did not predict a greater risk of development of leukemia. No consistent relationship was demonstrated between the occurrence of chromosome abnormalities and the development of myeloid metaplasia and/or myelofibrosis, which was observed in 42% of the patients. The chromosome abnormalities followed a nonrandom pattern, and those most frequently observed were trisomies for 1 q, 8, 9, or 9p and deletion of 20q. Deletions seem to be common and were found in 14 patients.

Adult↗

PubMed1987

Cytogenetic studies and in vitro colony growth in patients with mastocytosis.

Cytogenetic analysis of bone marrow cells and in vitro growth for bone marrow granulocytic-macrophage stem cells have been performed in 13 patients with mastocytosis, six with systemic mastocytosis, and seven with urticaria pigmentosa. Clones with chromosome abnormalities were found in five patients. The number of clusters and/or colonies after seven days in culture was increased in seven patients, compared with the growth in a control group. Three patients with chromosome abnormalities showed an abnormal growth pattern, yet exhibited normal peripheral blood values. Two patients with systemic mastocytosis had clones with chromosome abnormalities and some abnormal hematological values. The proportion of patients with chromosome abnormalities and an abnormal growth pattern was higher among these patients with mastocytosis than in healthy control subjects. These results may be of interest when discussing the origin of mast cell disorders and indicate an association with the myeloproliferative disorders.

Bone Marrow↗

PubMed1986

Trisomy 1q in polycythemia vera and its relation to disease transition.

Clinical and cytogenetic details of 12 patients with polycythemia vera and complete or partial trisomy of the long arm of chromosome 1 are reported. All patients had trisomy for at least the segments 1q22 to 1qter. The 1q or material from 1q was translocated to another chromosome in eight patients. This was chromosome 9 in four patients, and those cases all had trisomy also for 9p. The trisomy 1q was found at the time of diagnosis in three patients, later during the polycythemic phase in five, and in four patients when they were first examined during a late stage of the disease. Acute leukemia or a myelodysplastic syndrome developed in eight of the 12 patients. Signs of advanced disease, eg, myeloid metaplasia or myelofibrosis, preceded the leukemia in four cases and was noted in one more patient. Trisomy 1q was the most frequent structural chromosome abnormality in patients with polycythemia vera. It is thus one of several nonrandom abnormalities that can appear at any stage of the disease. It seems to occur with higher frequency in patients with myelofibrosis and/or leukemia, but it is not a specific characteristic of these complications.

Adult↗

PubMed1986

Malabsorption of vitamin B12 in dermatitis herpetiformis and its association with pernicious anaemia.

Serum vitamin B12 concentrations were determined in 129 patients and a pentagastrin test performed in 116 patients with dermatitis herpetiformis (DH). Low serum vitamin B12 levels were found in 27 patients (21%) and achlorhydria in 30. Forty-two patients with achlorhydria and/or vitamin B12 deficiency were subjected to further haematological and gastrointestinal investigations. Functional or morphological involvement of the small intestine was seen in almost all patients with vitamin B12 deficiency but, in addition, atrophic gastritis resulting in defective secretion of intrinsic factor (pernicious anaemia) was found in 8 cases (7% of all DH patients). Thus, a low vitamin B12 level in DH patients should result in a careful gastrointestinal examination as both an atrophic gastritis and a coeliac-like enteropathy have further clinical implications.

Achlorhydria↗

PubMed1986

Cyanocobalamin absorption in the elderly: results for healthy subjects and for subjects with low serum cobalamin concentration.

We examined the intestinal absorption of cyano[57Co]cobalamin from a non-protein-bound test dose given to 38 subjects from a population of elderly. The subjects were 76 years old and were apparently free from conditions known to affect cyanocobalamin absorption. Their gastric mucosal function was normal, as judged from determinations of serum gastrin and pepsinogen I. The urinary excretion of radioactivity during the first 24 h was 24(SD 7)%, range 8.6 to 45.2%, corresponding to a health-associated reference interval of 10 to 38%. The results indicate that cyanocobalamin absorption does not decline during normal aging. Duplicate studies were performed in another 20 subjects (70-81 years old) from the same population study; these subjects had a serum cobalamin concentration less than 130 pmol/L. The imprecision (CV) was 23%.

Aged↗

PubMed1986

The bone marrow in urticaria pigmentosa and systemic mastocytosis. Cell composition and mast cell density in relation to urinary excretion of tele-methylimidazoleacetic acid.

The bone marrow sections from five normal subjects and 18 patients with mastocytosis were examined to establish criteria to distinguish urticaria pigmentosa from systemic mastocytosis. Nine patients had increased numbers of mast cells in bone marrow sections stained with a long toluidine blue staining technique specific for mast cells, whereas five patients exhibited increased numbers of mast cells on May-Grünwald-Giemsa-stained smears of bone marrow. A positive correlation between the number of mast cells in sections of the bone marrow and the urinary excretion of the main histamine metabolite tele-methylimidazoleacetic acid was found. In ten of the examined bone marrow specimens, focal lesions containing mast cells, lymphocytes, and eosinophils appeared. The presence of these focal lesions together with either an increased number of mast cells in bone marrow sections and/or increased urinary excretion of telemethylimidazoleacetic acid is considered diagnostic of systemic mastocytosis. No patient exhibited myeloproliferative condition or other major hematologic abnormality.

Adult↗

PubMed1985

Karyotypic evolution in Ph-positive chronic myeloid leukemia in relation to management and disease progression.

In a prospective study of 32 patients with chronic myeloid leukemia the frequency of chromosome abnormalities in addition to the Philadelphia chromosome (Ph) increased when the disease progressed. Before metamorphosis, 10 patients (31%) had developed additional abnormalities. Such abnormalities were present in three of them at the time of diagnosis; in the other seven, they were detected late in the chronic phase. New clonal abnormalities heralded or accompanied a more malignant phase of the disorder, usually a blastic leukemia. During metamorphosis, 78% of the patients had additional abnormalities, which in 68% of these cases comprised at least one of +8, +22q- or i(17q). Clones with additional abnormalities disappeared in eight cases, either spontaneously or in association with cytostatic therapy during the chronic or blastic phase. Involvement of chromosome #8, usually in the form of a trisomy, was found in 7 of 12 patients treated with busulfan, but was not found in any of the 10 hydroxyurea-treated patients, of whom 8 were splenectomized early during the chronic phase. Cells from the spleen, obtained by fine needle aspiration or splenectomy were cytogenetically examined in 18 cases during the chronic phase, but abnormalities in addition to the Ph were noted in only one patient, who was examined in the late chronic phase. The same abnormalities were present in bone marrow cells of this patient.

Adult↗