PubMed Health⌕ Search

Biomedical subjects

T G Abrahamsen

Publications and source records attributed to T G Abrahamsen.

At least 19 recordsLinked to original sources
PubMed2006

Oral administration of a new soluble branched beta-1,3-D-glucan is well tolerated and can lead to increased salivary concentrations of immunoglobulin A in healthy volunteers.

The soluble branched yeast beta-1,3-D-glucan (SBG) belongs to a group of carbohydrate polymers known to exert potent immunomodulatory effects when administered to animals and humans. A new oral solution of SBG has been developed for local application to the oropharyngeal and oesophageal mucosa in order to strengthen the defence mechanisms against microbial and toxic influences. In the present study oral administration of SBG has been investigated primarily for assessment of safety and tolerability in an early phase human pharmacological study (phase I). Eighteen healthy volunteers were included among non-smoking individuals. The study was an open 1:1:1 dose-escalation safety study consisting of a screening visit, an administration period of 4 days and a follow-up period. Groups of six individuals received SBG 100 mg/day, 200 mg/day or 400 mg/day, respectively, for 4 consecutive days. The dose increase was allowed after a careful review of the safety data of the lower dose group. No drug-related adverse event, including abnormalities in vital signs, was observed. By inspection of the oral cavity only minor mucosal lesions not related to the study medication were seen in seven subjects. Repeated measurements of beta-glucan in serum revealed no systemic absorption of the agent following the oral doses of SBG. In saliva, the immunoglobulin A concentration increased significantly for the highest SBG dose employed. SBG was thus safe and well tolerated by healthy volunteers, when given orally once daily for 4 consecutive days at doses up to 400 mg.

Administration, Oral↗
PubMed2005

Pneumococcal conjugate vaccine followed by pneumococcal polysaccharide vaccine; immunogenicity in patients with ataxia-telangiectasia.

The immunodeficiency in Ataxia-telangiectasia (A-T) is characterised by low T and B cell counts, low levels of IgE, IgA and/or IgG2, and especially low levels of pneumococcal antibodies. The 23-valent pneumococcal polysaccharide vaccine (PPV23) has previously been shown not to be effective in A-T, but these patients are capable of making protective antibodies to other vaccines such as diphtheria and tetanus toxin, promising effect of the seven-valent pneumococcal conjugated vaccine (PCV7). Nine A-T patients and 25 age and sex matched controls were vaccinated with both PCV7 and PPV23, and three A-T patients were vaccinated with PCV7 only. In the A-T patients, no significant increase in pneumococcal antibody levels were observed after the single PCV7, while the subsequent PPV23 vaccination resulted in a significant increase in antibody levels to the PPV23 mix, as well as to serotype 4, 14, 19F and to the geometric mean of serotype 4, 6B, 14, 18C, 19F, 23F which increased from median 0.2 (range 0.1-0.5) microg/mL to 0.6 (0.2-1.5) microg/mL (P= 0.014). Compared to the patients' baseline levels, the vaccinations induced a 1.5- to 7-fold increase in antibodies to the six different serotypes tested. The increases in pneumococcal antibody titres were lower than those observed in the controls (9- to 34-fold increase). The results are valuable in planning the care of A-T patients, using PCV7 to trigger and PPV23 to booster the immune response and possibly prevent severe pneumococcal disease.

Adolescent↗
PubMed2004

Tumour necrosis factor receptor superfamily member 6 gene mutation detection by denaturing high-performance liquid chromatography.

Denaturing high-performance liquid chromatography (DHPLC) was evaluated as a tool for diagnostic screening of polymorphisms in the tumour necrosis factor receptor superfamily member 6 (TNFRSF6) also known as CD95, Apo-1 or Fas gene. Exons 1-9 of the TNFRSF6 gene were amplified from genomic DNA of 38 individuals, of which three were known to carry mutations in the TNFRSF6 gene. The TNFRSF6 gene amplicons were analysed for heterozygosity by DHPLC. Samples that displayed heterozygous variation by DHPLC were further analysed by sequencing. Comparison of DHPLC analysis with sequencing results showed an overall 100% concordance for samples in which heterozygosity was detected by DHPLC. Importantly, DHPLC was in all cases able to demonstrate the presence or absence of mutations in exon 9 encoding the death domain of the TNFRSF6 gene, which have been implied as the most frequent genetic cause of autoimmune lymphoproliferative syndrome. Comparison of DHPLC analysis with sequencing results showed an overall 100% concordance for samples in which heterozygosity was detected by DHPLC. In conclusion, DHPLC is a suitable method for the detection of genetic variation in the TNFRSF6 gene.

Base Sequence↗
PubMed2004

The impact of an early truncating founder ATM mutation on immunoglobulins, specific antibodies and lymphocyte populations in ataxia-telangiectasia patients and their parents.

Eleven Norwegian patients (aged 2-33 years, seven males and four females) with Ataxia-telangiectasia (A-T) and their parents were investigated. Five of the patients were homozygous for the same ATM mutation, 3245delATCinsTGAT, a Norwegian founder mutation. They had the lowest IgG2 levels; mean (95% confidence interval) 0.23 (0.05-0.41) g/l versus 0.91 (0.58-1.26) g/l in the other patients (P = 0.002). Among the 11 A-T patients, six had IgG2 deficiency, six had IgA deficiency (three in combination with IgG2 deficiency) and seven had low/undetectable IgE values. All patients had very low levels of antibodies to Streptococcus pneumoniae 0.9 (0.4-1.4) U/ml, while normal levels were found in their parents 11.1 (8.7-13.4) U/ml (P < 0.001). A positive linear relationship between pneumococcal antibodies and IgG2 (r = 0.85, P = 0.001) was found in the patients. Six of 11 had diphtheria antibodies and 7 of 11 tetanus antibodies after childhood vaccinations, while 4 of 7 Hemophilus influenzae type b (Hib) vaccinated patients had protective antibodies. Ten patients had low B cell (CD19+) counts, while six had low T cell (CD3+) counts. Of the T cell subpopulations, 11 had low CD4+ cell counts, six had reduced CD8+ cell counts, and four had an increased portion of double negative (CD3+/CD4-/CD8-) gamma delta T cells. Of the 22 parents (aged 23-64 years) 12 were heterozygous for the ATM founder mutation. Abnormalities in immunoglobulin levels and/or lymphocyte subpopulations were also observed in these carriers, with no correlation to a special ATM genotype.

Adolescent↗
PubMed2003

Cerebral venous thrombosis and Escherichia coli infection in neonates.

AIM: To present a possible association between cerebral venous thrombosis (CVT) and infection with Escherichia coli. METHODS: Four neonates with deep CVT occurring during an E. coli infection are presented. RESULTS: In these patients the thrombotic disease was found by Doppler ultrasonography. The thrombosis involved at least the sagittal sinus and the transverse sinus according to subsequent MRI scans. The E. coli strains did not produce verotoxin or haemolysin. Disseminated intravascular coagulation was not demonstrated. Three patients presented with seizures. At discharge, all of the patients had signs of neurological damage, but two of them have improved significantly since then. None of the patients has had recurrent (venous) thrombosis. CONCLUSION: E. coli infections in neonates may predispose to CVT, a finding that has clinical implications.

Escherichia coli↗
PubMed2001

Modulation of C3 gene expression in HepG2 human hepatoma cells.

Inflammation elicits an acute phase response, which includes changes in plasma concentrations of a number of cytokines, reflecting changes in their gene transcription in the liver. In this study, the induction of complement factor 3 (C3) was investigated in HepG2 cells, a human hepatoma cell line often used as a model system for cytokine-dependent expression of acute phase proteins of the liver. By using a very sensitive RT-PCR assay, the amount of mRNA for C3 was measured after induction with lipopolysaccharide (LPS) and interleukin-6 (IL-6). Both substances were found to up-regulate C3 gene expression. C3 mRNA level was lower in LPS-treated cells compared to IL-6 induction and also reached maximum expression at an earlier time point. These findings suggest a coordinate stimulation of C3 expression in the hepatocytes, which then maintains the host response to infectious agents.

Carcinoma, Hepatocellular↗
PubMed2001

V(D)J recombination defects in lymphocytes due to RAG mutations: severe immunodeficiency with a spectrum of clinical presentations.

Severe combined immunodeficiency (SCID) comprises a heterogeneous group of primary immunodeficiencies, a proportion of which are due to mutations in either of the 2 recombination activating genes (RAG)-1 and -2, which mediate the process of V(D)J recombination leading to the assembly of antigen receptor genes. It is reported here that the clinical and immunologic phenotypes of patients bearing mutations in RAGs are more diverse than previously thought and that this variability is related, in part, to the specific type of RAG mutation. By analyzing 44 such patients from 41 families, the following conclusions were reached: (1) null mutations on both alleles lead to the T-B-SCID phenotype; (2) patients manifesting classic Omenn syndrome (OS) have missense mutations on at least one allele and maintain partial V(D)J recombination activity, which accounts for the generation of residual, oligoclonal T-lymphocytes; (3) in a third group of patients, findings were only partially compatible with OS, and these patients, who also carried at least one missense mutation, may be considered to have atypical SCID/OS; (4) patients with engraftment of maternal T cells as a complication of a transplacental transfusion represented a fourth group, and these patients, who often presented with a clinical phenotype mimicking OS, may be observed regardless of the type of RAG gene mutation. Analysis of the RAG genes by direct sequencing is an effective way to provide accurate diagnosis of RAG-deficient as opposed to RAG-independent V(D)J recombination defects, a distinction that cannot be made based on clinical and immunologic phenotype alone.

Alleles↗
PubMed2001

Recovery of filamentous fungi from water in a paediatric bone marrow transplantation unit.

In order to determine whether water or water-related surfaces are a reservoir for opportunistic filamentous fungi, water sampling in the paediatric bone marrow transplantation (BMT) unit of the National Hospital University of Oslo, Norway was performed. During a six-month period 168 water samples and 20 samples from water-related surfaces were taken. The water samples were taken from the taps and showers in the BMT unit and from the main pipe supplying the paediatric department with water. In addition, 20 water samples were taken at the intake reservoir supplying the city of Oslo with drinking water. Filamentous fungi were recovered from 94% of all the water samples taken inside the hospital with a mean colony forming unit (cfu) count of 2.7/500mL of water. Aspergillus fumigatus was recovered from 49% and 5.6% of water samples from the taps and showers, respectively (mean 1.9 and 1.0cfu/500mL). More than one third (38.8%) of water samples from the main pipe revealed A. fumigatus (mean 2.1cfu/500mL). All water samples taken at the intake reservoir were culture positive for filamentous fungi, 85% of the water samples showed A. fumigatus (mean 3.1cfu/500mL). Twenty-five percent of water-related surfaces yielded filamentous fungi, but A. fumigatus was recovered from only two samples. We showed that filamentous fungi are present in the hospital water and to a lesser extent on water-related surfaces. The recovery of filamentous fungi in water samples taken at the intake reservoir suggests that the source of contamination is located outside the hospital.

Air Microbiology↗
PubMed2000

[Salmonella infection from turtles].

Small turtles are asymptomatic carriers of Salmonella. Infants are particularly at risk of clinical infection. We describe an eight months old boy who became sick with Salmonella. The family had two turtles. Salmonella Abony was found in faeces from the child and in samples from both turtles. Commercial distribution of reptiles is prohibited in Norway. However, illegal import from other countries where no such ban exist is common. There are an estimated 10,000 pet reptiles in the Oslo region, most of them are turtles. More than 90% of turtles may be carriers of Salmonella. Many owners of turtles are not aware of the risk of salmonellosis from their pets.

Animals↗
PubMed2000

[Tuberculosis in Norwegian children--diagnostic challenges].

BACKGROUND: Each year, 20-25 Norwegian children below the age of 18 are diagnosed with tuberculosis in Norway. MATERIAL AND METHODS: As a demonstration of various difficulties in the work-up and diagnosis of tuberculosis, we present eight infected children aged 15 months to 10 years. RESULTS: Children often contract the infection from adults and may develop serious manifestations including miliary tuberculosis and meningitis. The symptoms are often not specific and tuberculosis may be mistaken for other diseases. Delay and inappropriate diagnostics may have deleterious consequences. INTERPRETATION: The main message is to start treatment upon clinical suspicion of tuberculosis. It is mandatory to sample the necessary biological material for microbiological tests before starting treatment.

Adult↗
PubMed2000

Primary immunodeficiency diseases in Norway.

This study represents the first national epidemiological survey of primary immunodeficiency diseases in Norway. Uniform questionnaires were sent out in April 1998 to all hospital departments considered relevant. As of February 1999, a total of 372 patients have been registered, of whom 69 patients are deceased. With a population of 4.45 million people, the total prevalence of primary immunodeficiency diseases in Norway February 1, 1999 is 6.82 per 100000 inhabitants. Distribution between the main immunodeficiency diagnoses is (a) antibody deficiencies 50.8%, (b) combined deficiencies included other immunodeficiency syndromes 12.4%, (c) complement deficiencies 21.0%, (d) phagocytic disorders 6.7%, (e) and immunodeficiency associated with other congenital diseases 9. 1%. Compared to previous reports from other European countries, there is a smaller proportion of antibody deficiencies due to few IgA deficiencies registered and a large proportion of complement deficiencies due to many patients with hereditary angioedema.

Adult↗
PubMed2000

Acremonium strictum fungaemia in a paediatric patient with acute leukaemia.

A 7-y-old boy with relapsed acute lymphatic leukaemia developed fungaemia due to Acremonium strictum, a fungus belonging to the group of the hyaline hyphomycetes. Initially, the fungus was misdiagnosed as Candida sp. due to the presence of abundant adventitious forms. At the time of diagnosis the patient was neutropenic and had a central venous catheter (CVC) in situ. The formation of an occlusive thrombotic mass in the v. subclavia dextra complicated the infection. Treatment consisted of amphotericin B, fluconazole, granulocyte colony-stimulating factor (G-CSF) and removal of the CVC. However the patient responded clinically only after the intravascular thrombus had been removed surgically. Amphotericin B, voriconazole and terbinafine showed high activity in vitro against the Acremonium isolate. A literature review revealed 5 other immunocompromised paediatric patients with a systemic or localized infection due to Acremonium spp.

Acremonium↗
PubMed2000

The analysis of the complement activation product SC5 b-9 is applicable in neonates in spite of their profound C9 deficiency.

Native complement factors and complement activation products were measured in healthy neonates (n = 72) and in a group of infants with premature prolonged rupture of the membranes (PPROM) without sepsis (n = 10). Vitronectin concentration in normal cord blood was not correlated with gestational age, and the median value was 86.0% of adult values. This was markedly higher than other native complement factors studied (factor B: 35.9%, C4: 45.1%, C3: 56.2%). The concentration of C9 showed a positive correlation with gestational age and was very low, 10.8% of normal adult values in cord blood and 8.3% in the patients. Fifteen percent of the neonates had C9 levels lower than 2% of adult values. The complement activation products Bb and SC5 b-9 were significantly elevated in the patients (159% and 130% of control values, respectively), indicating alternative and terminal pathway activation. In contrast, C4 bc and C3 bc levels were not increased. The maximum amount of SC5 b-9 which could be generated in the neonatal sera by cobra venom factor was highly correlated with C9 concentration (rs = 0.86, p = 0.0001) The profound C9 deficiency found in neonates is correlated with gestational age, limits the capacity to form bacteriolytic C5 b-9 (m) and may predispose for severe invasive bacterial infection. The plasma level of SC5 b-9 under normal conditions was very low, only 0.3% (0.1%-3.0%) of the values obtained after CVF activation of the same samples. Therefore, we suggest that the analysis of SC5 b-9 is applicable also in neonates, in spite of their extremely low C9 levels.

Bacteremia↗
PubMed1999

[Utilization of anti-infective agents in pediatric departments in health region 2].

Children are often treated with antiinfective drugs, both in and out of hospital, but few studies of antiinfective drug use in paediatric departments have been published. We have analysed the dispensing of antiinfective drugs from hospital pharmacies to all eight paediatric departments in south-eastern Norway (Health region 2) during the years 1990-95. The total consumption of antiinfective drugs, measured by the number of defined daily doses (DDD), did not increase during the study period, though the total costs for such drugs increased by 48% for all eight departments. In 1995 the antiinfective drug use varied between 15 and 30 defined daily doses per 100 bed days. The total use of cephalosporins increased significantly. For vancomycin, antifungal drugs and antiviral agents, both consumption and cost increased in several departments. Knowledge of the total use of antiinfective drugs may be important when evaluating treatment regimens, especially with regard to microbial resistance.

Anti-Bacterial Agents↗
PubMed1999

Antibiotic susceptibility of blood culture isolates after nearly two decades with netilmicin and ampicillin in neonatal septicaemia.

The aim of the study was to investigate the in vitro antibiotic susceptibility of blood culture isolates after almost 20 years with ampicillin and methicillin as empirical treatment for neonatal septicaemia. All blood culture isolates and their antibiograms obtained in a single tertiary neonatal intensive care unit from 1 January 1989 to 31 December 1994 were reviewed. Two hundred and six blood cultures from 181 infants containing 223 bacterial and 11 fungal isolates were identified during 4416 admissions. Fifteen (6.7%) of the bacterial isolates were resistant to ampicillin and netilmicin. Fourteen per cent of the staphylococcal spp. were susceptible to penicillin while more than 90% were susceptible to netilmicin. The coagulase-negative staphylococci (CONS) were resistant to netilmicin, methicillin and gentamicin in 12%, 49% and 65%, respectively. Eighty-nine per cent of the methicillin-resistant CONS were susceptible to netilmicin as opposed to 17% to gentamicin (p<0.001). Except for one strain of Acinetobacter sp., all Gram-negative bacteria were susceptible to netilmicin. Our data show that the ampicillin-netilmicin combination still provides a high in vitro coverage (93%) against bacteria identified in blood cultures from newborns in our unit. Netilmicin has a significantly better in vitro effectiveness against CONS than gentamicin.

Ampicillin↗
PubMed1999

C-reactive protein (CRP) response patterns in neonatal septicaemia.

C-reactive protein (CRP) is an unreliable diagnostic tool in the early diagnosis of neonatal septicaemia. However, serial measurements have been shown to be useful in monitoring the effectiveness of treatment. The aim of the present study was to investigate whether a specific CRP response pattern to different groups of pathogens could be identified during treatment of neonatal septicaemia. Serial CRP measurements from day 1 to 4 in monomicrobial blood culture-proven episodes of septicaemia were reviewed. In 4416 admissions, 180 out of 206 positive blood cultures were monomicrobial; 121 monomicrobial septic episodes were eligible for final analysis of the CRP response during treatment. A low median (M) value (day 1 to 4) was identified in coagulase-negative staphylococci (CONS) (M=23 mg/l), contrasting with high median values in Staphylococcus aureus (M=58 mg/l), group B streptococci (M=51 mg/l), Escherichia coli (M=51 mg/l) and Candida species (M=76 mg/l) (p<0.001). Median CRP values in the two groups were different for each of the treatment days 1 to 4 (p<0.001). An increase (p<0.001) in CRP during the 24 h before initiation of treatment was a sign of late-onset CONS septicaemia. In episodes where antimicrobial treatment failed, CRP levels were moderately elevated the day prior to treatment start and increased continuously thereafter, whereas successful treatment was generally accompanied by a decline in CRP in less than 4 days. The CRP response to CONS is significantly less pronounced than to other commonly encountered pathogens in neonatal septicaemia. A rise in CRP beyond the third day of empirical treatment should give rise to a suspicion of fungal infection or ineffective antibacterial treatment.

Bacteremia↗