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Biomedical subjects

E Ostergaard

Publications and source records attributed to E Ostergaard.

At least 19 recordsLinked to original sources
PubMed1999

Vaccination of infants with a four-dose and a three-dose vaccination schedule.

Swedish infants were vaccinated with diphtheria, tetanus and pertussis toxoids, inactivated poliovirus vaccine and a Haemophilus influenzae type b - tetanus toxoid conjugate vaccine at 2, 4, 6 and 15 months (US vaccination program, 'US arm', n=118) or at 3, 5 and 12 months of age (Swedish vaccination program, 'Swedish arm', n=103). The antigen amounts in the diphtheria and tetanus vaccines were higher in the Swedish than in the US arm while the amounts in the other vaccines were the same in both arms. There were no serious side effects. Local reactions increased with the numbers of doses but did not differ significantly between the groups. Serum was obtained at 2, 7, 15 and 16 months in the US arm and at 3, 6, 12 and 13 months of age in the Swedish arm. A fifth serum was obtained in both groups at 4 yr of age. For vaccines with the same antigen amount the following was observed: a. three doses at 2, 4 and 6 months were more immunogenic than two doses at 3 and 5 months; b. the third dose in the Swedish arm was more immunogenic than the third dose in the US arm; c. the fourth dose in the US arm induced higher antibodies than the third dose in the Swedish arm (except for pertussis toxin antibodies that were similar in both groups) and the differences tended to remain at the age of 4 yr. Children in the Swedish arm received a higher diphtheria toxoid dose (25 Lf) than in the US arm (15 Lf) which led to higher diphtheria toxin antibodies in the Swedish arm at comparable ages. Children in the Swedish arm received a higher tetanus toxoid dose (7 Lf) than in the US arm (6 Lf). Tetanus antibodies were similar at comparable ages. In conclusion, the immunogenicity of vaccines in infancy can be improved by increasing the number of doses, by prolonging the intervals between doses and by increasing the antigen amount in the vaccine.

Antibodies, Bacterial↗
PubMed1997

Infant botulism. The first culture-confirmed Danish case.

Infant botulism is caused by intestinal colonization by Clostridium botulinum, C. barati or C. butyricum. Infant botulism has only rarely been reported outside the USA. A 3-month-old boy developed constipation, lethargy, feeding difficulties and descending, severe, symmetric weakness. He was breastfed but had also been fed honey. Supportive care led to complete recovery. The serum was positive for C. botulinum toxin type A-F (mouse toxin neutralization assay). A strain of C. botulinum producing toxin type A and E was identified in the stool. C. botulinum was identified in a jar of honey of the same brand as the honey fed to the patient.

Botulinum Toxins↗
PubMed1996

Intensive chemotherapy in childhood myelodysplastic syndrome. A comparison with results in acute myeloid leukemia.

Myelodysplastic syndrome (MDS) in children is often considered as a variant of acute myeloid leukemia (AML) and frequently treated as such. However, there are very few reported data on the outcome following AML treatment. We analyzed 20 consecutive cases of de novo MDS treated in Denmark according to the NOPHO AML protocols. The results were compared with those obtained in 31 children with de novo AML treated with the same protocols, and with the outcome in 10 children with MDS who received allogeneic bone marrow transplantation (BMT) without prior AML therapy. Distinction between MDS and AML was made morphologically according to the FAB criteria. All children were followed for at least 37 months. The proportion of complete remission in MDS and AML was 35 percent vs 74 percent. (P = 0.005), resistant disease 25 percent vs 10 percent (P = 0.14), death in cytopenia 40 percent vs 16 percent (P= 0.06), and 3-year survival 15 percent vs 35 percent. (P = 0.11), respectively. Duration of treatment-related cytopenia was similar in MDS and AML, except for a longer period of leukopenia in MDS following the second course of induction. Seven of 10 MDS children receiving BMT without prior chemotherapy are long-term survivors. Our data suggest that conventional AML regimens are associated with a low rate of complete remission, a high risk of death in cytopenia, and a limited curative potential in childhood MDS. Allogeneic BMT was in contrast associated with a high survival rate. BMT may, at least in some patients, be performed successfully without prior induction chemotherapy. The different response to therapy in MDS and AML may reflect fundamental biological differences between the two conditions.

Acute Disease↗
PubMed1995

Transient pancytopenia preceding acute lymphoblastic leukemia (pre-ALL).

Pancytopenia followed by a period of spontaneous recovery may precede the diagnosis of acute lymphoblastic leukemia (pre-ALL). Although both pre-ALL and myelodysplastic syndromes are preleukemic in a strictly temporal sense, there are several marked differences between the two conditions. We present eight children with pre-ALL who represented 2% of all cases of childhood ALL. The bone marrow was normo- or hypocellular with increased reticulin fibrosis during the pre-ALL phase. No cytogenetic abnormalities were found at the pre-ALL phase, but had developed at the time of overt leukemia in four of the six children examined. Based on the findings in our patients and on cases reported in the literature, we argue that pre-ALL is likely to represent a paraneoplastic syndrome early in the leukemic development that might be mediated via inhibitory properties related to clonally expanding but still cytogenetically normal cells. The findings may indicate a multistep pathogenesis of ALL.

Adolescent↗
PubMed1994

The effects of wound infiltration with bupivacaine versus saline on postoperative pain and opioid requirements after herniorrhaphy.

In a prospective, double-blind, placebo-controlled study, twenty-eight healthy, male patients, aged 20-69 years, scheduled for unilateral elective inguinal herniorrhaphy ad modum Bassini were randomized to receive postoperative infiltration of the surgical wound with either bupivacaine 0.25%, or isotonic saline. General anaesthesia was induced with thiopentone 3-5 mg.kg-1 and alfentanyl 10 micrograms.kg-1, and maintained with alfentanyl 5 micrograms.kg-1 15 min and N2O/O2. After herniorrhaphy, the internal fascia was infiltrated with bupivacaine 0.25% or saline, 10 ml. After closure of the external fascia, the subcutaneous tissue was infiltrated with bupivacaine 0.25% or saline, 15 ml on both sides of the surgical wound. Pain at rest, during mobilisation and during cough was significantly decreased in patients receiving bupivacaine compared to placebo. Median time to first request for morphine was increased from 25 min to 135 min, and the consumption of supplementary morphine during the 24 h study period reduced from four to two doses of 0.1 mg.kg-1 iv or 0.125 mg.kg-1 im, in patients who received bupivacaine compared to placebo.

Adult↗
PubMed1994

Evaluation of the antimicrobial effects of sodium benzoate and dichlorobenzyl alcohol against dental plaque microorganisms. An in vitro study.

Evaluation of antimicrobial agents is based on in vivo and in vitro studies. The minimum inhibitory concentrations (MICs) of sodium benzoate and dichlorobenzyl alcohol to 115 strains of plaque microorganisms were determined by a broth-dilution method. Sodium benzoate did not inhibit growth of any gram-positive cocci (MIC > 106,590 microM). MICs for Porphyromonas gingivalis and two strains of Treponema socranskii were 26,650 microM. The MIC of dichlorobenzyl alcohol to the reference strain of Actinobacillus actinomycetemcomitans was 723 microM and to P. gingivalis, two strains of T. socranskii, and Candida albicans 1,446 microM. MICs for other organisms were 2,892 to 5,784 microM. Saliva samples from 10 volunteers, collected at various times after toothbrushing with a dentifrice containing 10% sodium benzoate and 0.3% dichlorobenzyl alcohol, were analyzed gas-chromatographically. Immediately after toothbrushing mean levels of sodium benzoate and dichlorobenzyl alcohol were 372,626 microM and 7,529 microM, respectively. After 5 min mean levels were 38,700 microM and 734 microM. In conclusion, the concentrations of both antimicrobials dropped rapidly during the first 30 min, but for 5-10 min they were high enough to inhibit growth of potential periodontal pathogens.

Adult↗
PubMed1992

A neutrophil-derived proteolytic inactive elastase homologue (hHBP) mediates reversible contraction of fibroblasts and endothelial cell monolayers and stimulates monocyte survival and thrombospondin secretion.

Human heparin-binding protein (hHBP) is a recently discovered proteolytically inactive neutrophil elastase homologue with sequence identity to azurocidin and CAP37. The protein has antibacterial properties and chemotactic activity toward monocytes. In the present work, we show that monocytes, cultured under serum-free conditions, developed morphological changes and formed multicellular aggregates 4 h after the addition of hHBP at a concentration of 10 micrograms/ml. However, after prolonged incubation (11 days) with unchanged medium, the cells spread again. The hHBP-treated cells had a two- to threefold increase in survival compared to control cells, measured using trypan blue as an indicator of living cells. Differentiation of the alive cells to macrophages was detected by changes in morphology, a threefold increase in protein content, and a three- to fourfold increase in acid phosphatase activity. When monocytes in parallel experiments were labelled with [35S]methionine de novo synthesis and secretion of thrombospondin in a dose-dependent manner was observed after 16 h, with half-maximal secretion at 2 micrograms hHBP/ml and a maximal 12-fold increase in secretion with respect to controls at 16 micrograms/ml. Supplementary labeling with [35S]sulfate revealed that the same monocytes down-regulated the secretion of a large proteoglycan (300-400 kd), apparently also with a half-maximal decrease rate at 2 micrograms/ml hHBP. Exposure of confluent fibroblast and endothelial cell monolayers to hHBP (10 micrograms/ml) in the absence of fetal calf serum resulted in cell contraction leaving gaps between cells, the phenomenon being recognizable within 4 h after addition of hHBP. Addition of fetal calf serum to a concentration of 10% completely restored the monolayers. A unique role of hHBP in host defense involving recruitment of monocytes and a key function of hHBP in neutrophil extravasation in response to inflammatory chemotactic signals such as leukotriene B4, complement peptide C5a, and N-formyl-methionyl-leucyl-phenylalanine are suggested.

Amino Acid Sequence↗
PubMed1992

Comparison of the effects of methoxysuccinyl-Ala-Ala-Pro-Val-chloromethyl ketone-inhibited neutrophil elastase with the effects of its naturally occurring mutationally inactivated homologue (HBP) on fibroblasts and monocytes in vitro.

The mature neutrophils in the circulation contain, besides the different proteases known for a long time, a recently discovered proteolytically inactive elastase homologue (HBP/CAP37/azurocidin). This homologue, which we have named HBP due to its strong affinity to heparin, is a chemoattractant for monocytes and has been shown to induce reversible detachment and contraction when added to monolayers of endothelial cells or fibroblasts. HBP may therefore play a pivotal role in leukocyte migration in response to inflammation. In this report a comparison of CH3O-Suc-Ala-Ala-Pro-Val-CH2Cl-inhibited elastase with HBP, its naturally occurring homologue selectively mutated in active serine and histidine, reveals that homotypic aggregation of monocytes and contraction of fibroblasts is specific for HBP. HBP induces thrombospondin secretion from monocytes four times as efficiently as the inhibited elastase, and the same molecule was found unable to compete for a specific saturable binding of HBP to monocytes with an apparent KD of 3 x 10(-8)M.

Amino Acid Chloromethyl Ketones↗
PubMed1991

Covalent structure of two novel neutrophile leucocyte-derived proteins of porcine and human origin. Neutrophile elastase homologues with strong monocyte and fibroblast chemotactic activities.

The covalent structures of two, novel, neutrophile, leucocyte-derived, strongly basic proteins of porcine and human origin have been determined by microsequencing in combination with time-of-flight plasma desorption mass spectrometry. The porcine protein primary structure of 219 amino acid residues was shown to contain 6 cysteine residues, 2 putative carbohydrate sites and 14% basic residues. The human protein contained 221 amino acid residues of which 8 were cysteine, 4 putative carbohydrate sites and 12% basic. A 47% direct sequence similarity to human neutrophile elastase was found, but due to mutations of two of the three amino acids in the catalytic triad, proteolytic activity is absent. Modelling and alignment studies unveil a close relationship of both proteins to the serine protease family, the greatest similarity being to those serine proteases present in granules from peripheral blood cells. Both proteins have been shown to be chemotactically active for monocytes and fibroblasts in vitro.

Amino Acid Sequence↗
PubMed1990

Cystic mesothelioma of peritoneum: occurrence in a man.

We report a case of cystic mesothelioma of the peritoneum in a 54-year-old man in whom cystic masses were removed twice by surgery at an interval of 2 years. The patient died of cardiac arrest shortly after the second operation for a concurrent unresectable colonic cancer. The pathogenesis of the disease is uncertain, but we consider it neoplastic of low grade malignancy.

Adenocarcinoma↗
PubMed1990

Hepatosplenic candidiasis in children with cancer. Three cases in leukemic children and a literature review.

Three children with acute leukemia presented with prolonged fever and neutropenia after cytostatic therapy, which was followed by abdominal pain, hepatomegaly, and hepatic dysfunction with raised serum alkaline phosphatase. Abdominal CT scan and ultrasound demonstrated multiple small lesions compatible with the hepatosplenic candidiasis syndrome. Liver biopsies showed microabscesses with a granulomatous appearance, but evidence of yeasts and pseudohyphae was present in 1 case only. Cultures were negative. Treatment with amphotericin B and 5-fluorocytosine was successful in two children. At autopsy, one child had signs of active infection. We reviewed the literature on 27 children with hepatosplenic candidiasis. Abdominal symptomatology and prolonged fever, despite antibiotic therapy, in a patient with previous or present neutropenia after cytotoxic exposure, should lead to a careful evaluation, including noninvasive imaging studies, open liver biopsy, and prompt aggressive antifungal treatment, the response to which requires close follow-up.

Adolescent↗
PubMed1990

Volvulus of the caecum. An evaluation of various surgical procedures.

To evaluate the various operations for caecal volvulus we reviewed 48 patients who were treated between 1948 and 1989. Six were treated conservatively (the volvulus resolved before operation), and the remaining 42 patients (43 operations) were treated by untwisting (n = 14, 2 early deaths); caecopexy (n = 13, no deaths); caecostomy (n = 3, 2 early deaths); or resection (n = 13, one early death). At follow up a mean of 11.8 years later (range 0.4 to 34) the numbers of patients who had remained free of symptoms were 6, 5, 1 and 9, respectively. We conclude that resection gives the best long term results with acceptable mortality and morbidity and should be the treatment of choice for caecal volvulus.

Adult↗
PubMed1988

Adenosine induction of rapid catabolism of adenine ribonucleotides and independent elevation of the ATP content in quiescent mouse fibroblasts.

The influence of adenosine on the ribonucleotide metabolism in quiescent BALB/c 3T3 cells was studied. The cellular adenine ribonucleotides were labelled by pretreating the cells with [2-3H]-adenine. After addition of adenosine to the cell cultures, the amount and radioactivity of the cellular purine ribonucleotides and the radioactivity of the purine compounds in the medium were determined. It appeared that adenosine gave rise both to rapid catabolism of adenine ribonucleotides with inosine 5'-monophosphate (IMP) as an intermediate and to expansion of the cellular adenosine 5'-triphosphate (ATP) pool. The maximal rates and the apparent activation constants for the two processes have been determined. Experiments with varying concentrations of coformycin (an inhibitor of adenosine 5'-monophosphate [AMP] deaminase and adenosine deaminase) and of 5'-amino-5'-deoxyadenosine (an inhibitor of adenosine kinase), respectively, showed that each compound may almost completely inhibit the adenosine-induced catabolism. This effect can be obtained under conditions where there was little or no effect by the two inhibitors on the rate of expansion of the cellular ATP pool. These results may best be explained by assuming that the process of expansion of the ATP pool is independent of the induced catabolism of adenine ribonucleotides, even though both processes seem to depend on the phosphorylation of adenosine to AMP. The total increase in the pool size of ATP and of guanosine 5'-triphosphate (GTP), both caused by adenosine, seems not to have regulatory effect on adenine ribonucleotide catabolism.

Adenosine↗
PubMed1988

Stress-induced blocking of cell division in the colchicine arrest technique.

Previous studies have shown that procedures commonly used in studies of cell population kinetics in laboratory animals cause a transient block of the entrance of cells into mitosis. The purpose of the present study was, therefore, to examine whether the handling of animals in conjunction with the administration of colchicine affects the results obtained by the metaphase arrest technique. Groups of rats were injected with colchicine or saline at 1300 h and sacrificed at regular intervals during the following 140 min. Histological sections of the palatal mucosa were produced and the number of metaphases was assessed in the epithelium. In both the saline-treated and colchicine-treated groups the numbers of metaphases decreased immediately after injection and reached a minimum within 30 min. After that time a transient increase was observed in the saline group, whereas the number of metaphases in the colchicine-treated group increased continuously during the experimental period. These results indicate that colchicine takes effect after a delay period of 30 min and that the handling procedures in conjunction with the administration of colchicine provoke a transient block of the entry of cells into mitosis. The second part of the study was designed in such a way that the number of metaphases collected during a 2 h period under the influence of stress induced by injection of colchicine could be compared with the number of metaphases collected during the same time period without the influence of stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Albinism↗
PubMed1987

Purification and characterization of an inducible mitochondrial DNA polymerase from Tetrahymena thermophila.

Treatment of the eukaryotic organism Tetrahymena with various types of DNA-damaging agents has been reported to cause a 35-fold induction of a mitochondrial DNA polymerase. We here report that the enzyme can be induced in large-scale cultures by exposure of the cells to thymine starvation and/or intercalating agents. The induced DNA polymerase has been purified to near homogeneity, with a specific activity of approx. 300,000 units/mg protein. The relative molecular mass of the active form of the enzyme is approx. 100,000, as determined by glycerol gradient sedimentation. The subunit structure has been analysed by SDS polyacrylamide gel electrophoresis of the highly purified preparation and by immunoprecipitation with a monoclonal antibody directed to the DNA polymerase. A polypeptide of Mr 47,000 has been observed to be a subunit of the enzyme. This corresponds to the size of the subunits suggested for mitochondrial DNA polymerase from chicken embryos and mouse myeloma cells.

DNA-Directed DNA Polymerase↗
PubMed1987

The effect of prolonged stress-inducing electrical stimulation on cell proliferation in rat palatal epithelium.

This study examines whether blocking of cell division by stress-inducing electrical stimulation can be maintained for a prolonged period of time and whether this results in the accumulation of a large number of cells ready to divide when the block is released. A total of 96 rats was subjected to electrical stimulation at intervals of 30 min for periods of 2, 4, 6 or 12 hr. Groups of animals were killed every second hour during these stimulation periods. After 2, 4 and 6 hr groups of animals were exempted from further stimulation and killed 2 or 4 hr later. After termination of the 12 hr stimulation period, groups of animals were killed every second hour during the succeeding 24 hr. Forty-eight animals were left undisturbed and served as controls. Two and a half hours prior to death, each of the experimental and control animals was injected intraperitoneally (i.p.) with colchicine. Histological sections of the palatal mucosa were prepared and the numbers of arrested metaphases were counted. The electrical stimulation for 2, 4, 6 and 12 hr consistently resulted in a reduced number of cells entering mitosis, indicating a blockade at the G2/M transition. However, with an increase in the length of electrical stimulation, an increasing number of cells passed the block, while a decreasing number entered mitosis during the first 4 hr following cessation of the stimulation. The sum of metaphases accumulated during the various stress periods and the following 4 hr was always similar and consistently lower than the number of metaphases accumulated in the control animals within the same time periods. This observation indicates that, during stress-inducing electrical stimulation and the succeeding 4 hr, only a defined number of cells can enter the mitotic phase. Thus, in addition to the block at the G2/M transition, there appears to be another block of cell division at an earlier stage in the cell cycle.

Animals↗