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Biomedical subjects

T G Abrahamsen

Publications and source records attributed to T G Abrahamsen.

At least 37 records · Page 2Linked to original sources
PubMed1998

Blood culture isolates during 6 years in a tertiary neonatal intensive care unit.

Blood culture results obtained in a single tertiary neonatal intensive care unit are reviewed. In 4416 admissions occurring over 6 y we identified 206 positive cultures (4.7/100 admissions) growing 234 bacterial and fungal isolates in 182 infants. Very early and early onset positive cultures comprised 17% and 22% each. Gram-positive bacteria dominated in very early (61%), early (91%) and late onset (78%) cultures with coagulase-negative staphylococci (CONS) as the most frequent isolate in all groups (22%, 46% and 55%, respectively). The 3 most frequent isolates following CONS were in very early onset cultures Escherichia coli (19%), anaerobic bacteria (17%) and group B streptococci (GBS) (14%), in early onset cultures Staphylococcus aureus (28%), Enterococci (7%), E. coli (6%) and Viridans streptococci (6%) and in late onset cultures S. aureus (15%), Candida species (8%) and E. coli (5%). Infants < or = 999 g birthweight, representing 6% of the admissions, contracted 37% of the positive blood cultures and nearly half (44%) of the CONS isolates. In these patients, a significant increase (p < 0.001) in the number of positive cultures/100 admissions and in the proportion of positive cultures in conjunction with an intravascular catheter were seen (p < 0.001). An intravascular catheter was more often present when CONS were isolated as compared to other organisms (p < 0.05). 23 positive cultures (11.2%), most frequently E. coli, were associated with a fatal outcome. Our microbiological pattern is dominated by a gram-positive flora, which is in agreement with recent European and North American reports, but differs from earlier Scandinavian studies in the proportion of CONS and GBS reported.

Blood Specimen Collection↗
PubMed1998

Familial disseminated infection due to atypical mycobacteria with childhood onset.

We describe two brothers of consanguineous Pakistani parents who lived in Norway and had disseminated infections due to nontuberculous mycobacteria. The first boy developed clinical signs of disseminated BCG infection after vaccination. He was successfully treated with antimycobacterial agents. Two and one-half years later, he developed disseminated Mycobacterium avium complex infection and died at 6 years of age. The second boy, born 5 years after the death of his brother, did not receive BCG vaccine. At 2 years of age, he developed disseminated M. avium complex infection. Because he responded only partly to specific chemotherapy, empirical interferon gamma treatment was added to the antimycobacterial regimen. After 2 years of combined therapy, his condition is stable. Studies of peripheral blood mononuclear cells from the second boy demonstrated reduced surface expression of the ligand binding chain of interferon gamma receptor 1. This defect explains the increased susceptibility to mycobacterial disease in the two brothers.

Age of Onset↗
PubMed1997

[Cytomegalovirus infection in neonates. Diagnosis and therapeutic experiences].

Approximately 0.5-1% of all newborns are born infected with cytomegalovirus (CMV), but of these only one out of ten show symptoms at birth, most often with hepatosplenomegaly, thrombocytopenia, and/or brain affection. Of the remaining nine, one may later develop sequelae with hearing loss and/or mental retardation. CMV infection may also be acquired perinatally or in the newborn period, and may cause pneumonia and/or sepsis, possibly also gastrointestinal symptoms like blood in the stool, and poor weight-gain. We have diagnosed CMV infection in ten neonates and infants, and describe these patients in terms of symptoms, diagnosis and treatment. Ganciclovir is being tested in clinical trials as a treatment for congenital CMV infection, and was given to two of our patients with apparently good results.

Antiviral Agents↗
PubMed1997

[Hemangioma and vascular malformations. Diagnosis and treatment].

The authors discuss the dilemmas associated with diagnosis and treatment of haemangiomas and vascular malformations. The complexity of these conditions too often sends the patients wandering from one specialist to another in search of an optimal therapeutic approach. We have established a multidisciplinary team to facilitate interspecialty communication on diagnosis, natural history, and therapy.

Arteriovenous Malformations↗
PubMed1997

Infection with human cytomegalovirus (HCMV) stimulates monocyte production of complement factor 3.

Complement biosynthesis in monocytes is stimulated by different microorganisms including Gram negative bacteria and yeasts. We have tested the effect of human cytomegalovirus (HCMV) on complement factor 3 (C3) production by cultured human monocytes. The monocytes were challenged with either a crude or a purified HCMV preparation obtained from the supernatant of HCMV-infected fibroblasts. When the monocytes were infected with 2 pfu/cell of virus and cultured for 2 days, the increase in C3 production compared to control ranged from 3% to 162%, median 62% (p < 0.01). However, crude HCMV was even more potent in stimulating C3 production, as the increase in C3 values ranged from 104% to 507%, median 247% (p = 0.001). This indicates the presence in the crude HCMV preparation of a substance which acts synergistically with HCMV on the C3 production. When monocytes were stimulated by lipopolysaccharide (LPS), a well known inducer of C3, infection with crude or purified HCMV did not further increase C3 production. Both HCMV and substances produced during the propagation of HCMV in fibroblasts are able to stimulate C3 production in monocytes. Complement production by inflammatory cells may be of importance in host resistance against viral infections.

Cell Line↗
PubMed1996

Direct growth suppression of myeloid bone marrow progenitor cells but not cord blood progenitors by human cytomegalovirus in vitro.

Recently, considerable interest has arisen as to use cord blood (CB) as a source of hematopoietic stem cells for allogenic transplantation when bone marrow (BM) from a familial HLA-matched donor is not available. Because human cytomegalovirus (HCMV) has been shown to inhibit the proliferation of BM progenitors in vitro, it was important to examine whether similar effect could be observed in HCMV-infected CB cells. Therefore, the effect of HCMV challenge on the proliferation of myeloid progenitors from BM and CB was compared using both mononuclear cells (MNC) and purified CD34+ cells. A clinical isolate of HCMV inhibited the colony formation of myeloid BM progenitors responsive to granulocyte-macrophage colony-stimulating factor (CSF), granulocyte-CSF, macrophage-CSF, interleukin-3 (IL-3) and the combination of IL-3 and stem cell factor (SCF). In contrast, colony growth of CB progenitors was not affected. In addition, HCMV inhibited directly the growth of purified BM CD34+ cells responsive to IL-3 and SCF in single cell assay by 40%, wheras the growth of CD34+ progenitors obtained from CB was not suppressed. The HCMV lower matrix structural protein pp65 and HCMV DNA were detected in both CB and BM CD34+ cells after in vitro challenge. However, neither immediate early (IE)-mRNA nor IE proteins were observed in infected cells. Cell cyclus examination of BM and CB CD34+ cells revealed that 25.7% of BM progenitors were in S + G2/ M phase wheras only 10.7% of the CB progenitors. Thus, a clinical isolate of HCMV directly inhibited the proliferation of myeloid BM progenitors in vitro wheras CB progenitors were not affected. This difference in the susceptibility of CB and BM cells to HCMV may partly be caused by the slow cycling rate of naive CB progenitors compared to BM progenitors at the time of infection.

Adult↗
PubMed1996

Home therapy with subcutaneous immunoglobulin infusions in children with congenital immunodeficiencies.

OBJECTIVES: Patients with congenital, humoral immunodeficiencies are usually treated with intravenous immunoglobulin infusions. Subcutaneous infusions have emerged as an alternative treatment modality also in children. Our institution has run a subcutaneous infusion home therapy program for 6 years, and the purpose of this report is to describe our experience with this regimen. METHODS: The subcutaneous therapy of eight patients with immunodeficiency (three with agammaglobulinemia, one with common variable immunodeficiency, one with severe combined immunodeficiency and bone marrow transplantation, and three with hyper-immunoglobulin M syndrome) was evaluated by chart review and a questionnaire answered by all the families. The infusions were given for at least 3 hours each week by a small syringe driver at home after the family had attended an intensive educational course at the hospital. RESULTS: The children were given a total of approximately 1100 infusions. They started at the age of 2 to 8 (mean, 4.5) years and received these infusions for 1.5 to 6 (mean, 3) years. By administering immunoglobulin doses from 58 to 149 (mean, 97) mg/kg per week, trough serum immunoglobulin G values from 5.2 to 9.6 (mean, 7) g/L were obtained. No serious infections occurred. Short-lasting, local side effects such as swelling and redness were frequently reported, but pain or systemic adverse reactions during or after the infusions were never encountered. CONCLUSIONS: Home therapy with subcutaneous immunoglobulin infusions in children with congenital immunodeficiencies is a feasible and safe treatment alternative.

Child↗
PubMed1995

Human polymorphonuclear leukocytes store large amounts of terminal complement components C7 and C6, which may be released on stimulation.

Secretion of the C factors C7, C6, and C3 by human polymorphonuclear leukocytes (PMNs) and PBMCs was studied by ELISA and immunoblot. The release of C7 and C6 by PMNs during 24 h of culture was 16-fold and 6-fold higher, respectively, than the C3 release, with median concentrations of 50.2 ng/ml, 18.3 ng/ml, and 3.1 ng/ml, respectively. In PBMC cultures, C release was considerably lower, and there was a different secretory pattern with a 6-fold higher release of C3 compared with C7 and C6. Stimulation with PMA led to a more rapid and complete secretion of the components to the culture media, whereas treatment with unopsonized Candida species did not affect the release. PMN release of C factors was not dependent on protein biosynthesis, and there was no indication of a selective uptake of C7 from serum as demonstrated by incubating PMNs from a subject with allotype C7 N in C7 M serum. Thus, the C components were probably produced by the PMNs or their bone marrow precursors before ex vivo culture. In cell lysates of freshly isolated cells, median C7, C6, and C3 contents of 1 x 10(7) PMNs were 149.7, 60.1, and 10.4 ng/ml, respectively, whereas the corresponding values for 1 x 10(7) PBMCs were 3.2, 2.6, and 14.6 ng/ml, respectively. The C6 and C7 were shown to incorporate into the terminal complement complex, and their molecular integrity was supported by identical m.w. to C6 and C7 present in normal serum. PMNs may represent a major source of C7 and C6 and may be more important than monocytes or macrophages in contributing terminal C components at a site of inflammation. This suggests a new role for the PMN as a C membrane attack modulator.

Candida↗
PubMed1995

Transforming growth factor beta modulates C3 and factor B biosynthesis and complement receptor 3 expression in cultured human monocytes.

Complement biosynthesis in monocytes is stimulated by different pathogens and modulated by a variety of cytokines, but little is known about the possible effect of transforming growth factor beta (TGF-beta) on this monocyte function. We therefore studied the effect of TGF-beta 1 and TGF-beta 2 on constitutive, lipopolysaccharide (LPS)- and Candida albicans-induced monocyte biosynthesis of complement components C3 and factor B. Under all three conditions, both forms of TGF-beta (20 ng/ml) induced a two- to fourfold increase in C3 concentration in monocyte supernatants harvested after 2 or 5 days of cell culture, an effect that was abrogated by cycloheximide. In contrast, constitutive and pathogen-induced production of factor B was suppressed by TGF-beta. The effects of TGF-beta on complement production were neutralized by a monoclonal anti-TGF-beta antibody. Moreover, TGF-beta suppressed the pathogen-induced release of granulocyte-macrophage colony-stimulating factor and down-regulated the expression of complement receptor 3 (CD11b/CD18), while the expression of CD11a/CD18, a related beta 2 integrin, was unaffected. These novel effects of TGF-beta emphasize the immunomodulatory significance of this cytokine.

Adjuvants, Immunologic↗
PubMed1995

A phase I and II trial of dose-intensified cyclophosphamide and GM-CSF in pediatric malignant brain tumors.

PURPOSE: Cyclophosphamide is commonly used in the treatment of children with malignant brain tumors. The purpose of this study was to develop a multicycle, high-dose intensity cyclophosphamide regimen with granulocyte-macrophage colony-stimulating factor (GM-CSF) and to assess its activity against malignant glioma and primitive neuroectodermal tumor (PNET). METHODS: Twenty-three patients with brain tumors, including 15 with malignant glioma and six with PNET, were enrolled. Cyclophosphamide (1.8-2.25 g/m2/day for 2 days i.v.; total dose 3.6-4.5 g/m2) was administered and was followed by recombinant human GM-CSF (5 micrograms/kg/day s.c.) on days 3-11 or until the absolute granulocyte count reached 1.5 x 10(9)/L. RESULTS: With a total of 83 cycles administered, the mean dose intensity of cyclophosphamide ranged from 1.5 g/m2/week through cycle 2 (22 patients) to 0.8 g/m2/week through cycle 8 (two patients). No activity was seen against malignant glioma, and five of six patients with PNET had partial responses. The mean duration of a neutrophil count of < 0.5 x 10(9)/L was only 8 days; the platelet recovery was substantially longer. Fever during neutropenia occurred in 54 of 83 cycles. One patient died from transfusion-related graft-versus-host disease. CONCLUSIONS: A cyclophosphamide regimen equal to twice the dose intensity of that used in conventional therapy was administered. The regimen was active against PNET but inactive against malignant glioma.

Adolescent↗
PubMed1995

Various Candida and Torulopsis species differ in their ability to induce the production of C3, factor B and granulocyte-macrophage colony-stimulating factor (GM-CSF) in human monocyte cultures.

The incidence of infections with Candida albicans and also with non-albicans yeast species is increasing rapidly, particularly in immunocompromised patients. Eight Candida and Torulopsis species were compared for their ability to stimulate production of complement components C3 and factor B by monocytes. In addition, the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) was determined, because this cytokine affects monocyte complement production. The highest ranked pathogenic yeasts, i.e., C. albicans, C. tropicalis and C. parapsilosis, were the most effective inducers of C3, factor B and GM-CSF production. C. krusei and T. glabrata showed intermediate activity, whereas C. kefyr, C. guilliermondii and T. candida had only a moderate stimulatory effect on C3 production and did not affect either factor B or GM-CSF release. The stimulated cytokine and complement production in response to the yeasts was highly variable in monocytes from different donors, but there was a consistent inverse relationship between C3 and GM-CSF concentrations in the monocyte supernates. This is in agreement with the previously described suppressive effect of GM-CSF on yeast-induced C3, but not factor B production. The monocyte responses elicited by a specific yeast species may be linked to its pathogenicity, and may also explain the predilection of some yeasts for particular underlying diseases.

Candida↗
PubMed1995

Polymyxin B stimulates production of complement components and cytokines in human monocytes.

Polymyxin B (PmB), an agent often used to neutralize the effects of bacterial lipopolysaccharide (LPS), was shown to exert a dose-dependent stimulatory effect on the biosynthesis of C3, factor B, interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in human monocytes. A low dose of PmB (1 to 5 micrograms/ml) efficiently suppressed the LPS-induced (1 or 100 ng/ml) production of IL-6, GM-CSF, and factor B, but not the C3 production induced by 100 ng of LPS per ml. A reduced level of GM-CSF may have contributed to the persisting high C3 concentrations and the apparent lack of LPS inhibition in the latter situation, since GM-CSF is an inhibitor of monocyte C3 biosynthesis.

Complement C3↗
PubMed1995

Intrathecal immune response in neonatal Flavobacterium meningosepticum meningitis.

Neonates are predisposed to serious infections such as meningitis, probably due to their immature host reaction to the pathogens. We have studied the intrathecal immune response in 2 newborns with Flavobacterium meningosepticum meningitis. They showed a significant elevation of immunoglobulin indices ( >1.10), also after the CSF had become sterile with a normalized cell count. In addition, an intrathecal increase and subsequent decrease of both C3dg and TCC (terminal complement complex) were observed in 1 patient. We conclude that immunoglobulin production and complement activation may occur in neonatal CSF.

Antibody Formation↗
PubMed1993

Severe congenital neutropenia: abnormal growth and differentiation of myeloid progenitors to granulocyte colony-stimulating factor (G-CSF) but normal response to G-CSF plus stem cell factor.

Several mechanisms have been proposed to explain the pathogenesis of severe congenital neutropenia (SCN); however, the mechanism(s) still remains unknown. In particular, clinical observations suggest that abnormal responsiveness of myeloid progenitors to hematopoietic growth factors (HGFs) is a possible mechanism. Therefore, to better define the status of hematopoietic progenitors in the bone marrow (BM) of patients with SCN, the responsiveness of myeloid progenitors to HGFs from two SCN patients was compared with the responsiveness of progenitors from healthy individuals. BM cells (BMCs) from the first SCN patient required higher (10- to 100-fold) concentrations of granulocyte colony-stimulating factor (G-CSF) to achieve maximal and half-maximal colony growth in vitro compared with BMCs from controls. In contrast, the dose-response of interleukin-3 (IL-3) and granulocyte-macrophage-CSF (GM-CSF) in colony formation was normal. Interestingly, IL-3, GM-CSF, and G-CSF at optimal doses showed reduced ability to induce neutrophil differentiation of BMCs from a SCN patient compared with BMCs from controls. Despite an abnormal responsiveness of mature myeloid progenitors to G-CSF in this SCN patient, myeloid progenitors responsive to the combination of stem cell factor (SCF) and G-CSF showed normal dose-response. In contrast to G-CSF alone, the combination of G-CSF and SCF induced the formation of neutrophils almost to the same extent compared with cultures of normal BMCs. Furthermore, also on BM progenitor cells obtained from the second patient with SCN, SCF highly synergized with G-CSF to promote neutrophil progenitor cell growth and differentiation in vitro. Thus, these results indicate that one mechanism of the pathogenesis in SCN patients is reduced responsiveness of neutrophil progenitor cells to G-CSF and that SCF can enhance the responsiveness of these cells to G-CSF.

Bone Marrow↗
PubMed1993

Granulocyte-macrophage colony-stimulating factor, but not macrophage colony-stimulating factor, suppresses basal and lipopolysaccharide-stimulated complement factor production in human monocytes.

Monocyte/macrophage contribution of C biosynthesis is important, particularly during inflammation. Since granulocyte-macrophage CSF (GM-CSF) and macrophage-CSF (M-CSF) exert a variety of stimulatory effects on monocyte/macrophage functions in vitro, we studied their impact on the biosynthesis of the C components C3 and factor B by human monocytes in culture. GM-CSF at doses of 10 ng/ml and higher inhibited the basal C3 synthesis. This effect was most pronounced when the cytokine was added to freshly isolated monocytes. No effect was found on the basal production of factor B. Furthermore, GM-CSF abrogated the LPS-stimulated production of both C3 and factor B. These suppressive effects were neutralized by a polyclonal anti-GM-CSF antibody. Moreover, when anti-GM-CSF was added to unstimulated or LPS-stimulated cells, their C3 production increased. This indicates that both spontaneous and LPS-triggered release of monocyte-produced GM-CSF has an autocrine function in regulating monocyte C3 biosynthesis. GM-CSF also down-modulated the expression of CD14 at an early stage of cell culture. This might be the mechanism through which the LPS-effects are suppressed because CD14 has been shown to be a LPS receptor. Contrary to this, M-CSF at doses of 100 U/ml and higher stimulated the synthesis of C3, whereas the basal production of factor B and the LPS-stimulated production of C3 and factor B were unaffected. Granulocyte-CSF (G-CSF) did not influence monocyte C biosynthesis, and neither anti-M-CSF nor anti-G-CSF influenced the LPS-induced C3 production. The effects of GM-CSF and M-CSF on C biosynthesis may be important in regulating the availability of C components during an inflammatory response, and these observations may also have implications for the clinical use of CSF.

Antigens, CD↗
PubMed1993

[Diagnosis and treatment of infections in a neonatal unit--viral infections, spirochete infections and toxoplasma infections].

Viral and protozoal infections are often suspected as causes of neonatal illness or congenital anomalies. The TORCH titer has traditionally been the foremost diagnostic tool in this context, but it is now becoming increasingly clear that this tool is inadequate, partly for conceptual reasons, but also because of the often uncritical way in which it is used. During a recent critical review of our routines and practices for diagnosis and treatment of neonatal infections we also revised our approach to the diagnosis and treatment of suspected pre- or perinatally acquired viral, spirochetal, and protozoal illnesses. The resulting guidelines, originally intended for our house staff, are presented here.

Humans↗