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Biomedical subjects

J Nielsen

Publications and source records attributed to J Nielsen.

At least 19 recordsLinked to original sources
PubMed2007

Hemodynamic effect of sustained pulmonary hyperinflation in patients after cardiac surgery: open vs. closed chest.

BACKGROUND: In a previous study, we showed that sustained pulmonary hyperinflation, i.e. a lung recruitment maneuver, after closure of the chest in patients undergoing cardiac surgery had significantly negative effects on the central hemodynamics. As elevated pleural pressure is believed to be a major cause of this cardiovascular impairment, we hypothesized that performing the sustained pulmonary hyperinflation under open chest conditions would affect the circulation less. METHODS: Patients undergoing cardiac by-pass surgery were included and sustained pulmonary hyperinflations (40 cmH(2)O airway pressure for 15 s) were performed immediately before and after closure of the sternum. Pulse contour cardiac output, heart rate, mean arterial pressure and pulse pressure variation were measured before, during and 1 min after the hyperinflations. Left ventricular dimensions were measured using trans-esophageal echocardiography. RESULTS: Cardiac output (CO) and mean arterial blood pressure (MAP) decreased significantly during the sustained pulmonary hyperinflation both with an open and closed chest (in parenthesis): CO by 50 (45)% and MAP by 19 (24)%. The left ventricular end-diastolic area was significantly reduced by 24 (33)%. One minute after the hyperinflation, all measured variables had returned to baseline values. No significant differences in the measured variables were found between the two conditions before, during or 1 min after the hyperinflation. CONCLUSION: Contrary to our hypothesis, sustained pulmonary hyperinflations with the chest open, i.e. before sternal closure, had similar negative effects on central hemodynamics as those performed with the chest closed, i.e. after sternal closure.

Aged↗
PubMed2006

Simulation model estimates of test accuracy and predictive values for the Danish Salmonella surveillance program in dairy herds.

The Danish government and cattle industry instituted a Salmonella surveillance program in October 2002 to help reduce Salmonella enterica subsp. enterica serotype Dublin (S. Dublin) infections. All dairy herds are tested by measuring antibodies in bulk tank milk at 3-month intervals. The program is based on a well-established ELISA, but the overall test program accuracy and misclassification was not previously investigated. We developed a model to simulate repeated bulk tank milk antibody measurements for dairy herds conditional on true infection status. The distributions of bulk tank milk antibody measurements for infected and noninfected herds were determined from field study data. Herd infection was defined as having either >or=1 Salmonella culture-positive fecal sample or >or=5% within-herd prevalence based on antibody measurements in serum or milk from individual animals. No distinction was made between Dublin and other Salmonella serotypes which cross-react in the ELISA. The simulation model was used to estimate the accuracy of herd classification for true herd-level prevalence values ranging from 0.02 to 0.5. Test program sensitivity was 0.95 across the range of prevalence values evaluated. Specificity was inversely related to prevalence and ranged from 0.83 to 0.98. For a true herd-level infection prevalence of 15%, the estimate for specificity (Sp) was 0.96. Also at the 15% herd-level prevalence, approximately 99% of herds classified as negative in the program would be truly noninfected and 80% of herds classified as positive would be infected. The predictive values were consistent with the primary goal of the surveillance program which was to have confidence that herds classified negative would be free of Salmonella infection.

Animals↗
PubMed2006

Polyol synthesis in Aspergillus niger: influence of oxygen availability, carbon and nitrogen sources on the metabolism.

Polyol production has been studied in Aspergillus niger under different conditions. Fermentations have been run using high concentration of glucose or xylose as carbon source and ammonium or nitrate as nitrogen source. The growth of biomass, as freely dispersed hyphae, led to an increase of medium viscosity and hereby a decrease in mass transfer, especially oxygen transfer. The consequence was a decrease in DOT and the occurrence of a switch between fully aerobic conditions and oxygen-limited conditions. Metabolite quantification showed that polyols were the main metabolic products formed and represented up to 22% of the carbon consumed in oxygen-limited conditions. The polyol concentration and the polyol pattern depended strongly on the environmental conditions. This is due to a complex regulation of polyol production and to the fact that each polyol can fulfill different functions. In this study, erythritol, xylitol, and arabitol were produced as carbon storage compounds when the flux through the PP pathway exceeded the need in ribulose-5-phosphate for the biomass synthesis. Glycerol, erythritol, and xylitol seem to be involved in osmoregulation. Mannitol was produced when the catabolic reduction of charge was high. Its production involves the enzyme NAD-dependent mannitol-1-phosphate dehydrogenase and seems to be the main cytosolic route for the NADH reoxidation during oxygen limitation.

Aerobiosis↗
PubMed2006

Ocular and airway symptoms related to organic acid anhydride exposure--a prospective study.

BACKGROUND: Organic acid anhydrides (OAA) are used as hardeners in epoxy resin systems. They are powerful sensitizers giving frequent rhinitis and asthma in exposed workers. Incidence of symptoms is unknown. Here we present the first prospective study on the associations between OAA exposure, symptoms, and effects of confounding factors. METHODS: All new employees in three plants handling OAA were followed for up to 8.5 years. Before the employment, a questionnaire reporting about symptoms of eyes and airways, smoking habits, and atopy was answered. The subjects were asked at regular medical examinations about work tasks and work-related symptoms. Serum was analysed for specific OAA antibodies. RESULTS: Mean exposures varied between 6 and 39 microg/m3. The incidence for work-related symptoms of the eyes, nose, pharynx, and lower airways was 91, 64, 46, and 31 per 1000 years of exposure, respectively. Symptoms were found frequently, even at mean exposure level at <10 microg/m3. Smoking and atopy increased the risk of symptoms. Immunoglobulin (Ig)E sensitized workers had a significant increased risk for symptoms of the eyes and pharynx and for running nose/sneezing. CONCLUSIONS: Organic acid anhydrides exposure is associated with frequent ocular and airway symptoms even at mean exposure levels at <10 microg/m3. There is an important need for establishment of an occupational threshold limit. A limit value of below 5 microg/m3 is proposed.

Adult↗
PubMed2006

Cardiac output--pulse contour analysis vs. pulmonary artery thermodilution.

BACKGROUND: The aims of this study were to determine the agreement between pulmonary artery thermodilution (PA-TD), transpulmonary thermodilution (TP-TD) and the pulse contour method, and to test the ability of the pulse contour method to track changes in cardiac output. METHODS: Cardiac output was determined twice before cardiac surgery with both PA-TD and TP-TD. The precision (two standard deviations of the difference between repeated measurements) and agreement of the two methods were calculated. Post-operatively, cardiac output was determined with the PA-TD and pulse contour methods, and the bias and limits of agreement were again calculated. Finally, in patients with heart rates below 60 beats/min or a cardiac index of less than 2.5 l/min/m2, atrial pacing was started and the haemodynamic consequences were monitored with the PA-TD and pulse contour methods. RESULTS: Twenty-five patients were included. The precisions of PA-TD and TP-TD were 0.41 l/min [95% confidence interval (CI), +/- 0.07] and 0.48 l/min (95% CI, +/- 0.08), respectively. The bias and limits of agreement between PA-TD and TP-TD were - 0.46 l/min (95% CI, +/- 0.11) and +/- 1.10 l/min (95% CI, +/- 0.19), respectively. Post-operatively, the bias and limits of agreement between the PA-TD and pulse contour methods were 0.07 l/min and +/- 2.20 l/min, respectively. The changes in cardiac output with atrial pacing were in the same direction and of the same magnitude in 15 of the 16 patients. CONCLUSION: The precision of cardiac output measurements with PA-TD and TP-TD was very similar. The transpulmonary method, however, overestimated the cardiac output by 0.46 l/min. Post-operatively, cardiac output measurements with the PA-TD and pulse contour methods did not agree, but the pulse contour method reliably tracked pacing-induced changes in cardiac output.

Adult↗
PubMed2006

Bacillus Calmette-Guérin vaccination and infant mortality.

When the bacillus Calmette-Guérin (BCG) vaccine was introduced in the 1920s, it was suggested that BCG occasionally had nonspecific beneficial effects on mortality beyond the specific protection against tuberculosis. Considering that BCG has since then become the most used vaccine in the world, surprisingly few studies have been undertaken into the effect of BCG on general mortality and morbidity. Recent studies suggest that BCG has beneficial nontargeted effects on general infant morbidity and mortality in low-income countries, often with the most pronounced effect among girls. These observational findings are supported by early trials in which children were randomized or alternated to BCG vaccination. Furthermore, a BCG scar and a positive tuberculin reaction are related to better survival among BCG-vaccinated children in low-income countries, especially for girls. The findings are not explained by frailty bias, in other words, that healthy children are more likely to receive BCG vaccination. A nonspecific, gender-differential effect of BCG on general infant mortality may have large implications for tuberculosis vaccine research and routine vaccination policy.

BCG Vaccine↗
PubMed2005

Experimental reproduction of postweaning multisystemic wasting syndrome (PMWS) in pigs in Sweden and Denmark with a Swedish isolate of porcine circovirus type 2.

An experimental model using 3-day-old snatch-farrowed colostrum-deprived piglets co-infected with porcine circovirus type 2 (PCV2) and porcine parvovirus (PPV) is at present one of the best methods to study factors affecting development of postweaning multisystemic wasting syndrome (PMWS). A Swedish isolate of PCV2 (S-PCV2) retrieved in 1993 from a healthy pig has been used in this model to reproduce PMWS in pigs from Northern Ireland. This virus has been present in the Swedish pig population for at least a decade without causing any known PMWS disease problems, despite its potential pathogenicity. The reasons for this are unknown, but could be related to genetics, absence of triggers for PCV2 upregulation (infectious agent and/or management forms) within Swedish pig husbandry. In order to confirm the pathogenicity of S-PCV2, Swedish and Danish pigs were experimentally infected with this isolate according to the established model. Swedish pigs were also infected with a reference isolate of PCV2 (PCV2-1010) to compare the severity of disease caused by the two isolates in Swedish pigs. Both Danish and Swedish pigs developed PMWS after the experimental infection with S-PCV2. Antibodies to PCV2 developed later and reached lower levels in serum from pigs infected with S-PCV2 than in pigs inoculated with PCV2-1010. In general, pigs infected with S-PCV2 showed more severe clinical signs of disease than pigs infected with PCV2-1010, but pigs from all PCV2-inoculated groups displayed gross and histological lesions consistent with PMWS. All pigs inoculated with PPV, alone or in combination with PCV2, displayed interleukin-10 responses in serum while only pigs infected with PPV in combination with PCV2 showed interferon-alpha in serum on repeated occasions. Thus, the pathogenicity of S-PCV2 was confirmed and a role for cytokines in the etiology of PMWS was indicated.

Animals↗
PubMed2005

The LuxR receptor: the sites of interaction with quorum-sensing signals and inhibitors.

The function of LuxR homologues as quorum sensors is mediated by the binding of N-acyl-L-homoserine lactone (AHL) signal molecules to the N-terminal receptor site of the proteins. In this study, site-directed mutagenesis was carried out of the amino acid residues comprising the receptor site of LuxR from Vibrio fischeri, and the ability of the L42A, L42S, Y62F, W66F, D79N, W94D, V109D, V109T and M135A LuxR mutant proteins to activate green fluorescent protein expression from a P(luxI) promoter was measured. X-ray crystallographic studies of the LuxR homologue TraR indicated that residues Y53 and W57 form hydrogen bonds to the 1-carbonyl group and the ring carbonyl group, respectively, of the cognate AHL signal. Based on the activity and signal specificity of the LuxR mutant proteins, and on molecular modelling, a model is suggested in which Y62 (corresponding to Y53 in TraR) forms a hydrogen bond with the ring carbonyl group rather than the 1-carbonyl group, while W66 (corresponding to W57 in TraR) forms a hydrogen bond to the 1-carbonyl group. This flips the position of the acyl side chain in the LuxR/signal molecule complex compared to the TraR/signal molecule complex. Halogenated furanones from the marine alga Delisea pulchra and the synthetic signal analogue N-(sulfanylacetyl)-L-homoserine lactone can block quorum sensing. The LuxR mutant proteins were insensitive to inhibition by N-(propylsulfanylacetyl)-L-homoserine lactone. In contrast, the mutations had only a minor effect on the sensitivity of the proteins to halogenated furanones, and the data strongly suggest that these compounds do not compete in a 'classic' way with N-3-oxohexanoyl-L-homoserine lactone for the binding site. Based on modelling and experimental data it is suggested that these compounds bind in a non-agonist fashion.

4-Butyrolactone↗
PubMed2005

Inflammatory response during hyperglycemia and hyperinsulinemia in a porcine endotoxemic model: the contribution of essential organs.

BACKGROUND: During euglycemia acute hyperinsulinemia diminishes the cytokine response to endotoxin [Lipopolysaccharide (LPS)] exposure. In this study we elucidated whether acute hyperglycemia and hyperinsulinemia modify the cytokine content in several organs during LPS challenge in a porcine model. METHODS: Pigs (35-40 kg) were randomized to either normoglycemia (group 1, n = 8) or hyperglycemia and hyperinsulinemia (group 2, n = 8), anesthetized and mechanically ventilated. Both groups received a 180-min intravenous infusion of LPS (total 10 microg kg(-1)). Groups 1 and 2 were clamped at plasma glucose concentrations of 5 mM and 15 mM, respectively. Group 1 maintained a baseline insulin level while the hyperglycemic group exhibited increased insulin levels. RESULTS: Circulating cytokines, cytokine mRNA and cytokine protein content were examined in the heart, liver, kidneys, lungs, spleen, adipose and muscle tissue. After LPS exposure, in both groups vast and equal plasma cytokines were elicited by approximately 70-5000-fold. A 10-fold higher level of IL-10, IL-6 and TNF-alpha protein was found in kidney tissue compared to the other organs together with a 3-10-fold increase of TNF-alpha in adipose tissue. However, cytokine mRNAs as well as organ function were without statistical difference between the groups. CONCLUSION: Endotoxemia elicited a pronounced cytokine response in both plasma and at organ level. The kidneys and adipose tissue showed the highest cytokine protein content. Acute hyperglycemia apparently counteracts the well-established anti-inflammatory effects of insulin on the inflammatory response in a LPS challenged porcine model. Whether the observation can be extrapolated to more long-term stress-exposure remains to be clarified.

Animals↗
PubMed2005

Atypical neuroleptic malignant syndrome caused by olanzapine.

OBJECTIVE: Neuroleptic malignant syndrome (NMS) is a rare syndrome with four main symptoms: rigidity, hyperthermia, altered mental status and autonomic instability. We report a patient with an atypical manifestation of NMS. METHOD: A single case was reported. RESULTS: A patient with pneumonia developed delirium and was treated with olanzapine and developed a NMS with fluctuating hyperthermia and autonomic instability during a month. Only slight rigidity was present. Creatine kinase was not elevated. The patient was severely agitated and manic. After discontinuation of olanzapine the patient showed no psychopathology or hyperthermia. CONCLUSION: NMS should be considered when patients treated with antipsychotics develop one or more symptoms of NMS.

Adult↗
PubMed2004

Incisional local anaesthesia versus placebo for pain relief after appendectomy in children--a double-blinded controlled randomised trial.

Incisional local anaesthesia is widely used for postoperative pain relief after surgery. We present the results of a double-blinded and randomised controlled study of incisional bupivacaine versus placebo in 68 children undergoing open appendectomy. The trial medicine (0.5 ml/kg) was infiltrated into the subcutis after wound closure. Patients with a weight below 40 kg received a bupivacaine concentration of 0.25 % and the patients above 40 kg a concentration of 0.5 %. During the first 24 hours after surgery the patients in the bupivacaine group received on average 0.065 mg morphine/kg and in the placebo group 0.073 mg/kg. This difference was not statistically significant. The patients in the bupivacaine group tended to experience pain relief for a longer period of time compared to the patients in the placebo group. However, the difference was not significant. In conclusion, the use of subcutaneous infiltration with bupivacaine in the wound after open appendectomy had no significant effect on the use of morphine during the first postoperative day in children.

Adolescent↗
PubMed2004

Seizures in a 77-year-old-woman after a bolus dose of remifentanil.

Seizures in patients with no history of epilepsy has been associated with administration of remifentanil in two previous case reports. We present a case where a bolus dose of remifentanil (50 micrograms/kg) was followed by a self terminating generalised tonic-clonic seizure in a patient admitted for acute hip surgery, and no previous history of epilepsy.

Aged↗
PubMed2004

Association of HLA-DQ5 and HLA-DR1 with sensitization to organic acid anhydrides.

BACKGROUND: Organic acid anhydrides are low molecular weight industrial chemicals, able to cause rhinoconjunctivitis and asthma associated with specific IgE against hapten-carrier protein conjugate. Only a proportion of exposed workers develop IgE-associated allergy to acid anhydrides. OBJECTIVE: We determined whether genetic susceptibility, in particular, HLA Class II alleles may be a risk factor. METHODS: We undertook HLA typing in 52 cases who had confirmed specific IgE and in 73 referents matched on site, age and duration of acid anhydride exposure identified in cross-sectional studies of workers exposed to hexahydrophthalic (HHPA), methylhexahydrophthalic (MHHPA) and methyltetrahydrophthalic (MTHPA) anhydrides. RESULTS: The linked alleles DQ5 (odds ratio [OR]=4.3; 95% confidence interval [95% CI]=1.7, 11) and DR1 (OR 3.0; 95% CI 1.2, 11) were more prevalent in cases than in referents. Within DQ5, DQB1(*)0501 was particularly frequent (OR 3.0; 95% CI 1.2, 7.4). CONCLUSION: DQB1(*)05 gene confers susceptibility to develop specific IgE antibodies against HHPA, MHHPA and a non-significant trend with MTHPA. DQB1(*)0501 is protective for other low molecular chemical sensitizers (isocyanates and plicatic acid) which may indicate varying affinities for the corresponding specific class II molecules.

Adult↗
PubMed2004

Reduced case fatality among hospitalized children during a war in Guinea-Bissau: a lesson in equity.

BACKGROUND: During a recent armed conflict in Guinea-Bissau, we observed a marked decline in the case fatality among hospitalized children at the only paediatric department in the country. AIM: To analyse the causes behind the observed fall in case fatality. MATERIAL: All children hospitalized at the only paediatric department in the capital of Guinea-Bissau. The war cohort comprised all children hospitalized during the war, which lasted from June 1998 to May 1999, and the peace cohort comprised all children hospitalized in the year preceding the war. As part of a longitudinal community study, we also registered all children being hospitalized from the Bandim Health Project's study area, including routinely collected information on socio-economic background factors. METHODS: The war cohort was compared with the peace cohort in terms of determinants for hospital case fatality. Through information in the community register, we examined post-hospital mortality in the 2 wk after discharge as well as socio-economic differences in recruitment during the war. Hospital case fatality was estimated by odds ratios and compared by multiple logistic regression. Community mortality risk was estimated by deaths per person years. RESULTS: The case fatality among children aged 0-14 y fell during the war (age-adjusted OR = 0.58; 95% CI: 0.50-0.68). There was a uniform reduction in case fatality among children hospitalized less than 7 d, while we observed no decline among children hospitalized longer. There were more children per bed during the war and mean hospitalization time was shorter, and post-discharge mortality also fell (mortality ratio (MR) = 0.57; 95% CI: 0.40-0.83). Adjustment for socio-economic confounders in recruitment during the war period made no difference to the estimated decline in case fatality. The decline in case fatality at the hospital was not explained by a general decline in mortality. Compared with the preceding year, the mortality ratio was 1.34 (1.20-1.51) in the Bandim Health Project's study area during the war. Adjusted for age, the decline in case fatality at the hospital was most marked for disadvantaged groups. For example, the general reduction in case fatality was 42% (95% CI: 11-63); however, children of mothers without any schooling experienced a reduction of 73% (95% CI: 27-90%), whereas the reduction was only 33% (95% CI: 14-61%) for children of mothers with school education. CONCLUSION: The decline in case fatality could be explained neither by a general decline in childhood mortality nor by changes in recruitment or discharge policy. The decline was therefore most likely due to improved treatment as a result of better availability of drugs funded by humanitarian aid and the presence of dedicated staff, which was offered relief food as compensation. Interventions improving case management may have a proportionately larger effect for poor families.

Adolescent↗
PubMed2003

Pyruvate decarboxylases from the petite-negative yeast Saccharomyces kluyveri.

Saccharomyces kluyveri is a petite-negative yeast, which is less prone to form ethanol under aerobic conditions than is S. cerevisiae. The first reaction on the route from pyruvate to ethanol is catalysed by pyruvate decarboxylase, and the differences observed between S. kluyveri and S. cerevisiae with respect to ethanol formation under aerobic conditions could be caused by differences in the regulation of this enzyme activity. We have identified and cloned three genes encoding functional pyruvate decarboxylase enzymes (PDCgenes) from the type strain of S. kluyveri (Sk- PDC11, Sk- PDC12 and Sk- PDC13). The regulation of pyruvate decarboxylase in S. kluyveri was studied by measuring the total level of Sk- PDC mRNA and the overall enzyme activity under various growth conditions. It was found that the level of Sk- PDC mRNA was enhanced by glucose and oxygen limitation, and that the level of enzyme activity was controlled by variations in the amount of mRNA. The mRNA level and the pyruvate decarboxylase activity responded to anaerobiosis and growth on different carbon sources in essentially the same fashion as in S. cerevisiae. This indicates that the difference in ethanol formation between these two yeasts is not due to differences in the regulation of pyruvate decarboxylase(s), but rather to differences in the regulation of the TCA cycle and the respiratory machinery. However, the PDC genes of Saccharomyces/ Kluyveromyces yeasts differ in their genetic organization and phylogenetic origin. While S. cerevisiae and S. kluyveri each have three PDC genes, these have apparently arisen by independent duplications and specializations in each of the two yeast lineages.

Aerobiosis↗
PubMed2003

The effect of CreA in glucose and xylose catabolism in Aspergillus nidulans.

The catabolism of glucose and xylose was studied in a wild type and creA deleted (carbon catabolite de-repressed) strain of Aspergillus nidulans. Both strains were cultivated in bioreactors with either glucose or xylose as the sole carbon source, or in the presence of both sugars. In the cultivations on single carbon sources, it was demonstrated that xylose acted as a carbon catabolite repressor (xylose cultivations), while the enzymes in the xylose utilisation pathway were also subject to repression in the presence of glucose (glucose cultivations). In the wild type strain growing on the sugar mixture, glucose repression of xylose utilisation was observed; with xylose utilisation occurring only after glucose was depleted. This phenomenon was not seen in the creA deleted strain, where glucose and xylose were catabolised simultaneously. Measurement of key metabolites and the activities of key enzymes in the xylose utilisation pathway revealed that xylose metabolism was occurring in the creA deleted strain, even at high glucose concentrations. Conversely, in the wild type strain, activities of the key enzymes for xylose metabolism increased only when the effects of glucose repression had been relieved. Xylose was both a repressor and an inducer of xylanases at the same time. The creA mutation seemed to have pleiotropic effects on carbohydratases and carbon catabolism.

Aldehyde Reductase↗