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Biomedical subjects

A Lindberg

Publications and source records attributed to A Lindberg.

At least 37 records · Page 2Linked to original sources
PubMed2001

Validation of a test for dams carrying foetuses persistently infected with bovine viral-diarrhoea virus based on determination of antibody levels in late pregnancy.

Our objective was to estimate, using a generalised linear mixed-model approach, the sensitivity and specificity of an indirect ELISA when used to identify dams pregnant with persistently bovine viral-diarrhoea virus (BVDV)-infected foetuses. Cows that had been tested for antibodies to BVDV with a positive result during their pregnancy and where the offspring had been tested for both antibody and virus were identified by accessing the Swedish BVD database and the official pedigree records. The resulting data set consisted of 2162 cow-calf pairs in 126 herds, of which 281 included virus-positive calves. The sensitivities and specificities at 12 different decision thresholds (corresponding to optical densities (ODs) between 0.5 and 1.6) were estimated using generalised linear mixed models (binomial error, logit link), in which the gold standard (the BVDV status of the calf) was included as a covariate. In each model, the dependent variable was the dichotomous test result at the decision threshold in question. There was a significant positive interaction between the calf's status and gestational stage in all 12 models--indicating that the sensitivity and specificity at any given decision threshold was improved when the the test was performed later in pregnancy. The test should be applied only when samples have been taken in late gestation--not before the seventh month in pregnancy. If applied during the last months of pregnancy, the point estimate of the sensitivity ranges between 0.94 and 1.0 as the decision threshold is moved from 1.0 and downwards to 0.7. Similarly, the specificity ranges between 0.39 and 0.67 as the decision threshold is moved from 0.8 and upwards to 1.1.

Animals↗
PubMed2001

Towards the rational design of Th1 adjuvants.

Finding adjuvants in order to enhance immune responses against target immunogens has been a major and recurrent issue for the vaccine industry. It is yet to be solved, most particularly in the context of a growing interest in designing new types of vaccines capable of eliciting Th1 immune responses. A review of synthetic adjuvants which have been (or are being) tested in clinical studies is presented. Importantly, recent advances in our understanding of the physiology of immune responses offer new avenues to design and test candidate adjuvants, based on either synthetic or natural molecules, with the aim to mimic and recapitulate pro-inflammatory signals initiating both innate and adaptative immune effector mechanisms. Thus, adjuvants of the future might be a mixture of molecules selected singularly for a capacity to attract, target or activate professional antigen presenting cells. Used as a combination, such molecules should facilitate antigen presentation by professional APCs and lead to a potent induction of T cell-mediated effector and immune memory mechanisms.

Adjuvants, Immunologic↗
PubMed2001

Symptoms related to obstructive sleep apnoea are common in subjects with asthma, chronic bronchitis and rhinitis in a general population.

The purpose of this study was to examine the prevalence of self-reported snoring, apnoeas and daytime sleepiness in relation to chronic bronchitis, recurrent wheeze, physician-diagnosed asthma and rhinitis. This was a questionnaire study in a representative sample of a general population. The study was a part of the Obstructive Lung Disease in Northern Sweden Studies (OLIN). A total of 5424 subjects aged 20-69 years, born on the 15th day of each month, participated in the study. Eligible answers were obtained from 4648 subjects (85.7%). Having snoring as a problem was reported by 10.7%. Among subjects with chronic bronchitis it was reported by 25.9%, with recurrent wheeze by 21.3%, with physician-diagnosed asthma by 17.9%, and with rhinitis by 14.7%. Relatives' concerns of witnessed apnoea was reported by 6.8% of all subjects, while among subjects with chronic bronchitis it was reported by 18.1%, with recurrent wheeze by 17.1%, with physician-diagnosed asthma by 14.3%, and with rhinitis by 9.1%. After correction for age, gender and smoking habits, chronic bronchitis, rhinitis, asthma, and current smoking were significantly related, with snoring as a problem and with relatives' concern of witnessed apnoeas. Symptoms of daytime sleepiness were significantly related with concern of witnessed apnoeas, chronic bronchitis, snoring as a problem, recurrent wheeze and age 50-59 years. In conclusion, respiratory symptoms and conditions affecting mainly the lower respiratory tract, such as chronic bronchitis and asthma, were related with symptoms common in obstructive sleep apnoea.

Adult↗
PubMed2001

Obstructive sleep apnoea syndrome is common in subjects with chronic bronchitis. Report from the Obstructive Lung Disease in Northern Sweden studies.

BACKGROUND: In previous studies we have found that subjects with bronchitis have a higher prevalence of 'snoring as a problem' than respiratory healthy subjects. OBJECTIVES: We aimed to study whether the high prevalence of snoring among subjects with bronchitis also represents a high prevalence of obstructive sleep apnoea (OSA). METHOD: Subjects in three age groups born 1919-1920, 1934-1935 and 1949-1950 had been identified as bronchitic in an earlier study (n = 471) and without respiratory symptoms (n = 108). Of the 91 subjects reporting snoring to be a problem, 70 were invited to participate in the study. Sleep investigation was performed in 52 of these 70 subjects. RESULTS: 'Snoring as a problem', predicted OSA to a similar degree in both bronchitic and respiratory healthy subjects. The estimated prevalence for obstructive sleep apnoea with an apnoea/hypopnoea index (AHI) 10 as the cut-off point and concomitant daytime symptoms such as daytime sleepiness or liability to nodding off during breaks in activity in the daytime, was 5.4% for bronchitic subjects and 2.3% for respiratory healthy subjects. Apnoea in addition to snoring predicted OSA better than did snoring alone. Age correlated significantly with AHI, and OSA was most common in the middle-aged group, 61-62 years old. CONCLUSION: OSA is twice as common in subjects with chronic bronchitis as in subjects free of pulmonary disease or symptoms.

Aged↗
PubMed2001

The potential of prediction models based on data from KIGS as tools to measure responsiveness to growth hormone. Pharmacia International Growth Database.

Various prediction models have been developed, based on data documented within KIGS (Pharmacia International Growth Database), for use in the growth hormone (GH) treatment of children with short stature resulting from GH deficiency (GHD) or other causes. In addition to the practical value of such models as part of a 'forward strategy' guiding GH treatment, we now propose that prediction models may also be useful for the identification of individual variance in responsiveness. In a comparison involving 1,800 children with idiopathic GHD (IGHD), 151 children who acquired GHD after treatment for medulloblastoma and 192 children with GHD accompanying craniopharyngioma, it was shown that the responsiveness to GH of patients with craniopharyngioma equalled that of IGHD patients, whereas patients with medulloblastoma were less responsive. These observations and the identification of 'good' and 'poor' responders to GH have practical clinical consequences (e.g. modification of treatment), and will, in the future, lead to the identification of those factors which determine the variability of sensitivity to GH. This will improve the efficacy and safety of GH treatment as well as reducing the costs involved.

Databases as Topic↗
PubMed2000

Recombinant viruses as a tool for therapeutic vaccination against human cancers.

Viral vectors can be used to express a variety of genes in vivo, that encode tumor associated antigens, cytokines, or accessory molecules. For vaccination purposes, the ideal viral vector should be safe and enable efficient presentation of expressed antigens to the immune system. It should also exhibit low intrinsic immunogenicity to allow for its re-administration in order to boost relevant specific immune responses. Furthermore, the vector system must meet criteria that enable its industrialization. The characteristics of the most promising viral vectors, including retroviruses, poxviruses, adenoviruses, adeno-associated viruses, herpes simplex viruses, and alphaviruses, will be reviewed in this communication. Such recombinant viruses have been successfully used in animal models as therapeutic cancer vaccines. Based on these encouraging results, a series of clinical studies, reviewed herein, have been undertaken. Human clinical trials, have as of today, allowed investigators to establish that recombinant viruses can be safely used in cancer patients, and that such recombinants can break immune tolerance against tumor-associated antigens. These promising results are now leading to improved immunization protocols associating recombinant viruses with alternate antigen-presentation platforms (prime-boost regimens), in order to elicit broad tumor-specific immune responses (humoral and cellular) against multiple target antigens.

Antigens, Neoplasm↗
PubMed2000

Apolipoprotein CII from rainbow trout (Oncorhynchus mykiss) is functionally active but structurally very different from mammalian apolipoprotein CII.

Apolipoprotein CII (apoCII) plays an important role in plasma lipid metabolism as an activator for lipoprotein lipase (LPL). We have amplified and sequenced apoCII cDNA from rainbow trout. Amino acid sequence analyses confirmed that this sequence corresponded to the protein that had apoCII activity. Northern blot analyses showed that apoCII mRNA was present in both liver and intestine, but the level in intestine was very low. Two major transcripts (800 and 600bp) were found. The predicted amino acid sequence consists of 112 amino acid residues, including the signal peptide. The mature peptide is seven residues longer than human apoCII (86 versus 79 residues) due to an extension at the amino-terminal end. The rainbow trout sequence showed an overall identity of only 20-25% to previously known apoCII sequences. The carboxy-terminal region (residues 51-79, human numbering) showed 35-45% identity to other apoCII sequences, while in the amino-terminal region, there was little if any identity and it was not possible to predict any long amphipathic, potentially lipid-binding alpha-helices. Trout apoCII was present in all lipoprotein fractions including LDL. At +10 degrees C trout plasma showed higher ability to stimulate LPL than human plasma. We conclude that apoCII from rainbow trout is in most parts structurally different from apoCII from other species, and that it is adapted to function at low temperature.

Amino Acid Sequence↗
PubMed2000

Nicotine-induced excitation of locus coeruleus neurons is blocked by elevated levels of endogenous kynurenic acid.

The present electrophysiological study shows that manipulation with endogenous brain kynurenic acid (KYNA) is able to affect the response of central noradrenergic neurons to nicotine. Previous studies have shown that systemically administered nicotine in low doses is associated with a marked, but short-lasting increase in the firing rate of rat noradrenergic neurons in the locus coeruleus (LC). This action of nicotine is of peripheral origin and finally mediated via a release of glutamate within the LC. KYNA is an endogenous glutamate receptor antagonist, which shows an uneven distribution in human brain. Previous studies have shown that a potent inhibitor of kynurenine 3-hydroxylase, PNU 156561A, is able to dose-dependently increase the levels of KYNA in brain. Anesthetized rats were given PNU 156561A in a dose that caused a 5-fold increase in brain KYNA levels after 3-6 hours (40 mg/kg, i.v. ). This treatment was found to abolish the increase in firing rate of LC neurons induced by nicotine (25-200 microg/kg, i.v.). The results of the present study show that an increased concentration of endogenous brain KYNA is able to inhibit the activation of central noradrenergic neurons by nicotine. In addition, our results highlight the role of endogenous KYNA in brain as a potentially important modulator of brain glutamatergic responses.

Animals↗
PubMed2000

Monoclonal anti-LPS inner core antibodies protect against experimental hematogenous Haemophilus influenzae type b meningitis.

This study tested the protective activity of antibodies to the LPS core of Haemophilus influenzae (Borrelli et al., Infect. Immun. 1995;63: 3683-92) in a hematogenous meningitis model. Meningitis was established by intraperitoneal inoculation of infant rats with H. influenzae type b (Hib). The severity of infection was determined by daily assessment of mortality, symptoms of disease and weight changes. Mortality occurred rapidly after infection with 10(5)cfu/rat and most animals died within 24 h. At a lower infection dose (10(4)cfu/rat) the rats survived, but developed symptoms of disease such as tremor, hypothermia, lethargy and anorexia within 12-72 h post challenge. Surviving animals showed decreased weight gain. Bacteremia was detected by daily blood-cultures in 10/10 rats and cleared 6 days after inoculation. The monoclonal anti-LPS antibody MAHI 3 was used in passive protection studies. MAHI 3 increased the survival in the high inoculum group (10(5)cfu/rat) from 10-17% in control animals to 60-90%. At the lower inoculum concentration (10(4)cfu/rat) MAHI 3 treatment reduced the symptoms and blood counts. Intraperitoneal injection of MAHI 3 was more effective than intranasal injection as shown by the effect on bacteremia. We conclude that anti-LPS antibodies can protect against mortality caused by hematogenous Hib infections in infant rats.

Animals↗
PubMed2000

Weaning of piglets. Effects of an exposure to a pathogenic strain of Escherichia coli.

The influence of weaning on day 32 and a simultaneous challenge with a pathogenic strain of Escherichia coli was studied in eight piglets. Another nine weaned but non-infected piglets were used as controls. The distribution of peripheral blood mononuclear cells (PBMC) into subpopulations, as well as their response when stimulated in vitro by pokeweed mitogen, changed in a similar manner during post-weaning in both groups. In contrast, superior responses were recorded for PBMC collected from the challenged pigs when stimulated in vitro with concanavalin A and with a heat-inactivated extract of the E. coli strain used for infection, respectively. Despite a successful colonization of the challenge strain, no clinical signs of disease were recorded. Nor did the daily weight gain or the number of E. coli, enterococci, or Clostridium perfringens excreted per gram of faeces differ between the groups. However, the weaning induced a marked decrease in the diversity of coliforms in individual piglets, which announced a reduced colonization resistance of that flora. Also, a decreased homogeneity between coliform floras of different piglets was observed following weaning. The decreased homogeneity indicated that different strains of E. coli were predominant in different animals, which may in turn facilitate the spread of pathogenic strains. The enteric changes were more pronounced and lasted longer in infected animals. Still, the influence of a sole pathogenic strain of E. coli was not enough to induce post-weaning diarrhoea.

Animals↗
PubMed2000

Interfacial adaptation of a Class II polyacid-modified resin composite/resin composite laminate restoration in vivo.

The aim of this in vivo study was to evaluate the interfacial adaptation of Class II resin composite open sandwich restorations with a polyacid-modified resin composite as a stress-absorbing layer (PMRC/RC). Twenty Class II box-shaped, enamel-bordered cavities were prepared in 10 premolars scheduled to be extracted for orthodontic reasons. An open PMRC/RC sandwich restoration was placed in 1 of the cavities of each tooth. The first layer, PMRC, in the proximal box extended to the periphery in the cervical part of the cavity. The following RC layers were placed with a horizontally incremental technique. The PMRC was excluded from the control cavity. The teeth were extracted after 1 month and the interfacial adaptation of the restorations was studied with quantitative scanning electron microscope analysis using a replicate technique. Gap-free interfacial adaptation was observed for the PMRC/RC and RC restorations in cervical enamel in 97% and 73%, respectively (P = 0.006). The gap-free scores for dentin were 87% and 64%, respectively (P = 0.022). Excellent interfacial adaptation was observed in both groups for the occlusal enamel 99% and 100%, respectively. The adaptation to occlusal enamel for the direct resin composite restorations was significantly better than to dentin or cervical enamel. A higher frequency of enamel fractures was observed parallel to the cervical margins compared to the occlusal. No dentin fractures were observed in the experimental groups. The PMRC/RC sandwich technique showed a statistically significant improved interfacial adaptation to dentin and cervical enamel in Class II enamel-bordered cavities. The clinical significance of the differences has to be evaluated.

Absorption↗
PubMed2000

Plasma pharmacokinetics of etoposide (VP-16) after i.v. administration to children.

The pharmacokinetics of etoposide (VP-16), a semi-synthetic derivative of podophyllotoxin, were studied in 16 pediatric patients (median age 8.3 years; range 4 months to 22 years) including two girls with Down's syndrome (DS). The drug was administered as infusions (1-3 h) in a wide range of doses (9-322 mg, corresponding to 32-210 mg/m2). The area under the plasma concentration versus time curve (AUC), dose normalized by the body surface area, was independent of age, while AUC normalized by the dose in mg/kg increased with increasing age of the patients. The interpatient variability of AUC, normalized for the dose in mg/m2, was 23% (CV) compared to 32% (CV) normalized for the dose in mg/kg. The terminal half-life time was 4.1 h (median value; range 2.0-7.8 h). The pharmacokinetics of etoposide in children with DS and chromosomally normal children were very similar with regard to systemic drug exposure and plasma half-life time. From the pharmacokinetic point of view it was therefore not necessary to make any dose modifications in the two girls with DS. The two DS patients did not experience any enhanced degree of toxicity from their etoposide treatments. The results support that dosing of etoposide to children should be based on body surface area.

Adolescent↗
PubMed2000

Toxins, butyric acid, and other short-chain fatty acids are coordinately expressed and down-regulated by cysteine in Clostridium difficile.

It was recently found that a mixture of nine amino acids down-regulate Clostridium difficile toxin production when added to peptone yeast extract (PY) cultures of strain VPI 10463 (S. Karlsson, L. G. Burman, and T. Akerlund, Microbiology 145:1683-1693, 1999). In the present study, seven of these amino acids were found to exhibit a moderate suppression of toxin production, whereas proline and particularly cysteine had the greatest impact, on both reference strains (n = 6) and clinical isolates (n = 28) of C. difficile (>99% suppression by cysteine in the highest toxin-producing strain). Also, cysteine derivatives such as acetylcysteine, glutathione, and cystine effectively down-regulated toxin expression. An impact of both cysteine and cystine but not of thioglycolate on toxin yield indicated that toxin expression was not regulated by the oxidation-reduction potential. Several metabolic pathways, including butyric acid and butanol production, were coinduced with the toxins in PY and down-regulated by cysteine. The enzyme 3-hydroxybutyryl coenzyme A dehydrogenase, a key enzyme in solventogenesis in Clostridium acetobutylicum, was among the most up-regulated proteins during high toxin production. The addition of butyric acid to various growth media induced toxin production, whereas the addition of butanol had the opposite effect. The results indicate a coupling between specific metabolic processes and toxin expression in C. difficile and that certain amino acids can alter these pathways coordinately. We speculate that down-regulation of toxin production by the administration of such amino acids to the colon may become a novel approach to prophylaxis and therapy for C. difficile-associated diarrhea.

Amino Acid Sequence↗
PubMed2000

Growth hormone and neurofibromatosis.

Data collected from 102 neurofibromatosis (NF) children with growth hormone (GH) deficiency (GHD) who were receiving GH replacement therapy were reviewed to assess the efficacy and safety of GH therapy in this condition. GH was administered at a mean dose of 0. 18 mg/kg/week. During the 1st year the median height velocity increased significantly from 4.2 cm/year before treatment to 7.1 cm/year, and the median height standard deviation score increased from -2.4 to -1.9. The response to therapy, however, was not as good as that observed in patients with idiopathic GHD. GH therapy did not influence the progression of any of the features of NF, including intracranial tumours, and was not associated with an excess of other adverse events. We conclude that GH treatment of NF patients with GHD is beneficial in terms of improved growth rate and is well tolerated.

Adolescent↗