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Biomedical subjects

K G Nielsen

Publications and source records attributed to K G Nielsen.

At least 19 recordsLinked to original sources

Effects of posture on postoperative pulmonary function.

BACKGROUND: Pulmonary morbidity is still a relevant complication to major surgery despite improvements in surgical technique and anaesthetic methods. Postoperative posture may be a pathogenic factor, but the effects of changes in postoperative posture on pulmonary function have not been reviewed. METHODS: Review of controlled, clinical trials evaluating postoperative pulmonary function in patients positioned in the supine vs. the sitting or standing position and patients positioned in the supine vs. the lateral position. Data were obtained from a search in the Medline and Cochrane databases (1966 - August 2002) and manually searched bibliographies of the identified papers. RESULTS: Eighteen papers met the inclusion criteria. Twelve studies evaluated the supine vs. the sitting or standing position and six studies evaluated the supine vs. the lateral position. Six of 12 studies found a positive effect on postoperative pulmonary function in the sitting or standing position compared with the supine. Thus, avoidance of the supine position may improve postoperative pulmonary function. Three of six studies showed a positive effect on postoperative pulmonary function of the lateral side compared with the supine. Thus, the lateral position has limited effects on pulmonary function. CONCLUSION: Changes of postoperative position from supine to sitting or standing are of major importance in the interpretation of postoperative pulmonary outcome studies and in future strategies to improve pulmonary outcome.

Functional Residual Capacity↗

Discriminative capacity of bronchodilator response measured with three different lung function techniques in asthmatic and healthy children aged 2 to 5 years.

The primary aim of this study was to quantify and compare bronchodilator responsiveness in healthy and asthmatic children aged 2 to 5 yr. The secondary aim of the study was to compare discriminative capacity (i.e., sensitivity, specificity, and predictive values of the reversibility test for the diagnosis of asthma) for each of the lung function tests applied in the study. Specific airway resistance (sRaw) as measured by whole-body plethysmography, respiratory resistance as measured with the interrupter technique (Rint), and respiratory resistance and reactance at 5 Hz (Rrs5, Xrs5, respectively) as measured with the impulse oscillation technique were assessed before and 20 min after inhalation of terbutaline from a pressurized metered-dose inhaler via a metal spacer by 92 children (37 healthy controls and 55 asthmatic subjects). The study of healthy children followed a randomized, double-blind, crossover design, whereas the study of asthmatic children was open. Baseline lung function was significantly decreased in asthmatic children as compared with healthy control subjects as reflected by all techniques used in the study. sRaw, Rint, and Rrs5, but not Xrs5, improved significantly with terbutaline as compared with placebo in healthy control subjects. Lung function improved to a significantly greater extent in asthmatic children than in control subjects as reflected by all methods. sRaw provided the best discriminative power of such a bronchodilator response, with a sensitivity of 66% and specificity of 81% at the cutoff level of a 25% decrease in sRaw after bronchodilator administration. In conclusion, bronchodilator response measured by sRaw allows a separation of asthmatic from healthy young children. This may help define asthma in this clinically difficult-to-manage group of young wheezy children. The sensitivity and specificity of the other methods used in the study were less than those of sRaw.

Administration, Inhalation↗

Bronchodilation and bronchoprotection in asthmatic preschool children from formoterol administered by mechanically actuated dry-powder inhaler and spacer.

We evaluated the bronchodilatory and the bronchoprotective effect of the long-acting beta(2)-agonist formoterol administered as dry powder from a mechanically actuated dry-powder inhaler (DPI) using spacer in 12 asthmatic children 2 to 5 yr of age. Lung function was measured as the specific airway resistance (sRaw) in a whole body plethysmograph. Hyperventilation of cold, dry air was used as bronchial challenge, and the responsiveness was estimated as change in sRaw. The bronchoprotective effect of formoterol Turbohaler 9 microg was compared with salbutamol 200 microg and placebo at 15 min, 4 and 8 h postdose in a randomized, double-blind, placebo-controlled, crossover study. All treatments were administered from DPI (Turbohaler) actuated mechanically into a spacer. Formoterol and salbutamol caused similar and significant bronchodilation at the first measurement 3 min postdose. Formoterol offered a sustained and stable bronchodilation for at least 8 h. Salbutamol provided significant bronchodilation for less than 4 h. Formoterol caused significant bronchoprotection of 80% for at least 8 h compared with placebo, and from 4 h onward compared with salbutamol. Bronchoprotection from salbutamol lasted less than 4 h. In conclusion, formoterol administered as dry powder in a single dose provided rapid and sustained bronchodilation and clinically significant bronchoprotection for at least 8 h in 2- to 5-yr-old asthmatic children. Furthermore, this study suggests that mechanical actuation of DPI using a spacer is effective for aerosol treatment of young asthmatic children.

Administration, Inhalation↗

Observer variability of lung function measurements in 2-6-yr-old children.

The aim of this study was to assess the within-observer and between-observer variability of lung function measurements in children aged 2-6 yrs. Two observers examined 22 asthmatic children independently according to a predefined protocol. Each observer obtained duplicate measurements of respiratory resistance by the interrupter technique (Rint), respiratory resistance (Rrs,5) and reactance (Xrs,5) at 5 Hz by the impulse oscillation technique and the specific airway resistance (sRaw) by whole body plethysmography. The within-subject SD (SDw) was not significantly different in the two observers. The ratio SDw between observers/mean SDw within observers was 0.94, 1.25, 1.35 and 2.86 for Xrs,5, Rrs,5, sRaw and Rint, respectively, indicating greater between-observer variability of the latter. The systematic difference between observers assessed by the difference between observer means (expressed as a percentage of their mean value) was 11, 7, 6 and 2% for Xrs,5, sRaw, Rrs,5 and Rint, respectively. These differences were statistically significant, except that for Rint. In conclusion, specific airway resistance, impulse oscillation technique and respiratory resistance assessed by the interrupter technique measurements in young children are subject to influence by the observer, and the random variability between observers appears to be particularly great for respiratory resistance assessed by the interrupter technique. The authors suggest that the between-observer variability should be investigated when evaluating novel methods for testing lung function.

Airway Resistance↗

Lung function response to cold air challenge in asthmatic and healthy children of 2-5 years of age.

The aim of the study was to assess feasibility, sensitivity, specificity, predictive value, and repeatability of cold, dry air challenge (CACh) as a diagnostic test for asthma in young children 2 to 5 yr of age. Response to a 4-min single-step isocapnic CACh was measured in 38 asthmatics and 29 control subjects. Specific airway resistance (sRaw) by whole body plethysmography was the primary outcome. In addition, lung function was measured as respiratory resistance by the interrupter technique (Rint) and respiratory resistance and reactance at 5 Hz (Rrs5, Xrs5) by the impulse oscillation technique. At baseline, lung function measures differed significantly between asthmatics and healthy control subjects. CACh was readily performed in young children. Response was expressed as change from baseline in numbers of within-subject standard deviation (SDw). Hyperresponsiveness defined as change in lung function of more than 3 SDw was detected by sRaw in 26 of 38 asthmatics versus 2 of 29 control subjects, by Rint in 12 of 38 asthmatics versus 1 of 29 control subjects, by Xrs5 in 9 of 38 asthmatics versus zero of 29 control subjects and by Rrs5 in 7 of 38 asthmatics versus 1 of 29 control subjects. Thus sRaw had the highest sensitivity (68%). Specificity ranged from 93 to 100%. The correlation coefficient between sRaw responses to CACh repeated within 8 wk was 96%. In conclusion, CACh is feasible in young children age 2 to 5 yr. Whole body plethysmography (sRaw) was superior in separating asthmatics from healthy control subjects. Change in sRaw in response to CACh may be used as a diagnostic test for asthma in young children.

Asthma↗

Bronchoprotection with a leukotriene receptor antagonist in asthmatic preschool children.

We hypothesized that a leukotriene receptor antagonist (LTRA) could provide bronchoprotection against the cold, dry air-induced response in asthmatic preschool children. In a randomized, double-blind, placebo-controlled crossover study, we examined the effect of the specific LTRA montelukast at 5 mg/d for 2 d on the bronchoconstriction induced by hyperventilation of cold, dry air in 13 asthmatic children 3 to 5 yr old. The bronchoconstriction was measured as the specific airway resistance (sRaw) in a whole-body plethysmograph before and 4 min after challenge with cold, dry air. The repeatability of the bronchoprotection was examined by repeating the placebo-controlled study in six of the 13 children. sRaw increased by an average of 46% (95% confidence interval [CI]: 30 to 63%) after placebo treatment and 17% (95% CI: 3 to 31%) after montelukast (p < 0.01). Eight of the children were receiving regular treatment with budesonide delivered by an inhaler with a spacer in a mean daily dose of 350 microg, but the bronchoprotection provided by montelukast was independent of concurrent steroid treatment. There was no convincing evidence of failure to respond, and the protective effect of montelukast was consistent upon repeated testing (p = 0. 02). We conclude that the LTRA montelukast provided clinically significant bronchoprotection against the effect of hyperventilation of cold dry air in asthmatic children 3 to 5 yr old. The bronchoprotection appeared to be homogeneous among the children, and seemed independent of steroid treatment. This suggests that LTRAs may be of therapeutic use in limiting clinical symptoms of asthma in young children.

Acetates↗

The effect of inhaled budesonide on symptoms, lung function, and cold air and methacholine responsiveness in 2- to 5-year-old asthmatic children.

We hypothesized that measurement of lung function (LF) and bronchial hyperresponsiveness (BHR) could serve as supplemental tools in evaluating the efficacy of treatment with inhaled corticosteroids in asthmatic children aged 2 to 5 yr. We studied 38 children (mean age: 53 mo; range: 35 to 71 mo) with moderately severe asthma in a single-center, randomized, double-blind, parallel-group, placebo-controlled study involving 8 wk of treatment. Budesonide (BUD) 400 microgram twice daily was administered via a pressurized metered-dose inhaler and metal spacer device. Symptom scores (SSc) and use of short-acting beta(2)-agonist were monitored with diary cards. LF in awake children was measured as the specific airway resistance (sRaw), using whole-body plethysmography; as resistance by the interrupter technique (Rint); and as resistance and reactance at 5 Hz (Rrs5, Xrs5) by the impulse oscillation technique. Cold air challenge (CACh) and methacholine challenge (MCh) were used to assess BHR. Children in the BUD group experienced significantly fewer night- and daytime symptoms (p < 0.05) and more symptom-free days (p < 0.05), but not nights (p = 0.07), than children in the placebo group. Daytime (p < 0.05) but not nighttime (p = 0.09) use of rescue medication and asthma exacerbation rates (3.7 versus 9.3 exacerbations/yr) (p = 0.006) were both in favor of BUD. LF measured with the Rint technique, Rrs5, and Xrs5 were significantly improved by BUD. BHR as measured by CACh improved significantly with BUD, whereas no improvement was found on MCh. In conclusion, inhaled BUD at a total dose of 800 microgram daily significantly improved SSc, asthma exacerbation rates, lung function, and BHR as assessed by CACh in asthmatic children aged 2 to 5 yr.

Administration, Inhalation↗

Radioiodine therapy for multinodular toxic goiter.

BACKGROUND: Radiolabeled iodine 131 therapy is used for treatment of multinodular toxic goiter, but long-term follow-up studies are lacking. METHODS: A prospective study of 130 consecutive patients (115 women) treated with 131I for multinodular toxic goiter and followed by evaluation of thyroid volume (determined using ultrasound) and thyroid function variables. RESULTS: The patients were observed for a median of 72 months (range, 12-180 months). Sixty-six patients received antithyroid drug pretreatment; 64 did not. Iodine 131 treatment (3.7 MBq/g thyroid tissue corrected to a 100% 24-hour 131I uptake) was given as a single dose in 81 patients, 2 doses in 38, and 3 to 5 doses in 11. One or 2 treatments cured 119 patients (92%), and 68 (52%) became euthyroid within 3 months after 131I treatment. The median 131I dose was 370 MBq (range, 93-1850 MBq). Forty-nine patients needing more than 131I dose had a reduction in median thyroid volume from 56 mL (range, 21-430 mL) to 44 mL (range, 15-108 mL), representing a 24% reduction related to the insufficient 131I dose. In all patients, the initial median thyroid volume of 44 mL (range, 16-430 mL) decreased to 25 mL (range, 8-120 mL) (P<.005), representing a median reduction of 43%, 24 months after the last 131I dose. Hypothyroidism evaluated using life-table analysis developed in 6% of patients who did not receive antithyroid pretreatment and 20% who did (P<.005) after a median of 42 months (range, 3-60 months), the total hypothyroidism frequency being 14% within 5 years of treatment. CONCLUSIONS: Ninety-two percent of patients with multinodular toxic goiter were cured with 1 or 2 treatments. The thyroid volume was reduced by 43%, with few side effects. Iodine 131 should be the choice of treatment in patients with multinodular toxic goiter.

Adult↗

Long-term effect of radioactive iodine on thyroid function and size in patients with solitary autonomously functioning toxic thyroid nodules.

OBJECTIVE: To investigate the long-term effects of radioiodine (131I) on thyroid function and size in patients with a solitary toxic thyroid nodule. DESIGN: Prospective study of patients treated for a solitary autonomous toxic nodule, followed by evaluation of thyroid volume and function. PATIENTS: Sixty-two consecutive patients followed for a minimum of 12 months (range 12-168, median 60). Seventeen patients received antithyroid drug treatment before 131I. MEASUREMENTS: Standard thyroid function variables and ultrasonically determined thyroid volume before as well as 0.75, 1.5, 3, 6 and 12 months after treatment, and then once a year were investigated. RESULTS: 131I treatment (3.7 MBq/g thyroid tissue corrected to a 100% 24-h 131I uptake) was given as a single dose in 53 patients; six needed two doses and another three were given 3-5 131I treatments. The median initial dose was 310 MBq (140-666) and the median total dose was 332 MBq (148-1576). In patients receiving one 131I treatment (n = 53) the total thyroid volume decreased significantly from a median of 40 ml (range 19-77) to 24 ml (8-50) within 3 months. This represented a median reduction of 35%. A further significant decrease was seen after 24 months to a total reduction of 45%. In patients given more than one dose the thyroid volume was reduced from a median of 45 ml (19-104) before treatment to 30 ml (14-50) after a follow-up of 60 months (9-132) after the last 131I treatment. Patients without antithyroid pretreatment, receiving one 131I treatment (n = 39) became euthyroid after a median of 1.5 months (0.75-9) after treatment. Seventy-five per cent were euthyroid within 3 months. In patients pretreated with antithyroid drugs and treated with one dose of 131I (n = 14) euthyroidism was achieved after a median of 12 months (0.75-24) after 131I treatment. Hypothyroidism developed in five patients (8%) after a median of 36 months (6-60) after 131I treatment. CONCLUSION: A cure-rate of 75% within 3 months is seen when treating autonomous solitary toxic thyroid nodules with 131I. The thyroid volume is reduced by 35% within 3 months and 45% after 2 years. Side-effects are few and consist of hypothyroidism in less than 10% with a median follow-up of 5 years. This treatment should be regarded as the standard treatment for this condition until prospective comparisons with surgery and ethanol injection therapy have been performed.

Adult↗

[Enzyme substitution in Gauscher disease].

Gaucher's disease is the most frequent inherited lysosomal storage disorder, displaying hepato-splenomegaly, thrombocytopenia, anaemia, and bone pain as characteristic features. Substitution with the modified enzyme alglucerase has revolutionized the treatment and prognosis of Gaucher's disease. Treatment in general and current trends in enzyme substitution therapy in particular are discussed.

Gaucher Disease↗

[Gaucher disease type 1--therapeutic results of enzyme substitution].

Gaucher's disease is the most common inherited lysosomal storage disorder, displaying hepato-splenomegaly, thrombocytopenia, anaemia and bone pain as characteristic features. Substitution therapy with a modified enzyme alglucerase has revolutionized the treatment and prognosis of Gaucher's disease. The first Danish patients treated with alglucerase are reported.

Adolescent↗

Gastrin and cholecystokinin of the bullfrog, Rana catesbeiana, have distinct effects on gallbladder motility and gastric acid secretion in vitro.

Many regulatory peptides form families with at least two homologous members. For several such families the divergence of the individual members from a common ancestor can be dated to early in vertebrate history. Cholecystokinin (CCK) and gastrin were originally identified in mammals. Recently, two distinct members of the CCK/gastrin family were identified in the bullfrog (Rana catesbeiana), termed CCK and gastrin. Frog gastrin is very similar to CCK in the region defining biological activity. To evaluate whether the two endogenous peptides have distinct properties, their effects were studied in typical target organs. While porcine gallbladder responded equally to frog gastrin-8 and CCK-8, EC50 values for stimulation of bullfrog gallbladder contractions were 490 nM (gastrin) and 69 nM (CCK). In contrast, gastrin appeared to be a more potent stimulant of acid secretion than CCK; the estimated EC50 values are 3.1 and 17.2 nM, respectively. Furthermore, gastrin had a significantly higher efficacy than CCK-8s. Thus, in spite of their close structural resemblance, there are clear differences between the two endogenous peptides in their action on gallbladder and gastric mucosa. It is concluded that there are distinct gastrin and CCK functions already at the amphibian level of evolution.

Amino Acid Sequence↗

Iohexol: effects on uptake of radioactive iodine in the thyroid and on thyroid function.

RATIONALE AND OBJECTIVES: The authors attempted to determine whether the use of nonionic contrast media causes uptake of iodine by the thyroid to be blocked and whether use of these agents could cause iodine-induced hyperthyroidism. MATERIALS AND METHODS: Twenty-eight persons, including 22 with thyroid disease, were included in the study. Subjects underwent computed tomography (CT) of the thyroid after injection of 100 mL of iohexol. Thyroid function variables were measured before CT scanning and 1 week and 1 month later. In 16 subjects, uptake of iodine-131 by the thyroid was measured before and 1 week after CT. RESULTS: I-131 uptake was reduced to 53.4% at 1 week after the injection of iohexol but became normal within a few weeks (followed up in one patient). An accelerated escape of I-131 from the thyroid was seen during the 1st days after the iohexol administration. Eight of 22 patients with an underlying thyroid disease had a temporary change in thyroid function. In four patients, the serum thyrotropin level was increased 1 week after the iohexol administration. In four other patients, temporary hyperthyroidism developed during the following months. CONCLUSION: Iohexol can be used in patients with an underlying thyroid disease, but close monitoring in the following months is necessary.

Adult↗

Clinical effect of Diskus dry-powder inhaler at low and high inspiratory flow-rates in asthmatic children.

In vitro studies with the Diskus inhaler at low and high flow rates show consistent doses of drug as fine particles <4.7 microm. The present study was designed to ascertain whether this in vitro flow independency translates into flow-independent clinical effect when the device is used by patients at low (30 L x min[-1]) and high (90 L x min[-1]) flow rates. A pilot study in 129 children aged 3-10 yrs demonstrated that 99% of children of 3 yrs and above can generate a flow > or = 30 L x min(-1) through the device, while 26% performed > or = 90 L x min(-1). Eighteen children aged 8-15 yrs with exercise induced asthma inhaled placebo or salmeterol 50 microg at either 30 L x min(-1) or 90 L x min(-1). Exercise challenges were carried out 1 h and 12 h after dosing. The maximum percentage fall in forced expiratory volume in one second (FEVI) after exercise 12 h after treatment was significantly less after salmeterol at either flow rates as compared to placebo. There was no significant difference in the protection from salmeterol on the day of low-flow inhalation versus the day of high-flow inhalation. Consistent in vitro fine particle dosing from the Diskus inhaler translates into a consistent clinical effect at low and high flow rates in children.

Adolescent↗

Controlled trial of inhaled budesonide in patients with cystic fibrosis and chronic bronchopulmonary Psuedomonas aeruginosa infection.

The efficacy and safety of anti-inflammatory treatment with inhaled glucocorticosteroids in patients with cystic fibrosis (CF) and complicating chronic Pseudomonas aeruginosa (P.a.) lung infection was studied in a placebo-controlled, parallel, double-blind single center trial. Active treatment consisted of budesonide dry powder, 800 microg twice daily, delivered from a Turbuhaler. The study period covered two successive 3-mo intervals between elective courses of intravenous anti-Pseudomonas antibiotics. Fifty-five patients entered the study, with a mean age of 20 yr and a mean FEV1 of 63% of predicted. Analysis of all patients entered, irrespective of trial adherence ("intention to treat"), showed a decrease in FEV1 in the first period of -0.032 L in patients on budesonide versus -0.187 L in patients on placebo (p = 0.08). The corresponding figures for the patients adhering to the protocol during the first period were -0.017 L versus -0.198 L (p < 0.05, confidence interval of the difference: -0.035 to +0.327 L). For all patients entered, as well as for patients adhering to the trial, there was always a trend in favor of budesonide, as judged by changes in FEV1 and FVC in both 3-mo periods. None of the patients had asthma, but the patients on budesonide had a mean improvement in histamine reactivity of +1.15 dose steps over the entire 6-mo period, as opposed to +0.017 dose steps in patients on placebo (p < 0.05). There was also a significant (p = 0.01) correlation between pre-trial histamine reactivity and the change in FEV1 in the first period in patients on budesonide. We conclude that inhaled glucocorticosteroids can be of short-term benefit in patients with CF and chronic P.a. infection and that those patients most likely to benefit from this treatment are patients with hyperreactive airways. Prolonged studies in larger number of patients are necessary to determine the long-term efficacy of this treatment.

Administration, Inhalation↗

Flow-dependent effect of formoterol dry-powder inhaled from the Aerolizer.

The output and size distribution of aerosols from dry powder inhalers are dependent on the flow rate through the device. Therefore, in an in vivo study, we examined the flow-dependency of the effect of formoterol when delivered from a dry powder inhaler, the Aerolizer, in a flow range relevant to schoolchildren. In a preliminary study comprising 126 asthmatic children aged 3-10 yrs, the relationship between age and peak inspiratory flow (PIF) rate through the Aerolizer was determined. Mean PIF was 104 L.min-1 and all children aged > 5 yrs performed a PIF > 60 L.min-1. Sixteen children aged 8-15 yrs with exercise-induced asthma (EIA) took part in the main trial comparing the protective effect of 12 micrograms formoterol inhaled at 60 and 120 L.min-1. The effect from high and low inspiratory flow was judged from the protective effect against EIA 12 h after drug administration. The decrease in forced expiratory volume in one second (FEV1) after exercise was 34% on the placebo day, but only 15% when formoterol was inhaled at the high flow rate. This difference was statistically significant. The decrease in FEV1 was 23% after treatment with formoterol inhaled at the low flow rate, that was not significantly different from placebo or from high-flow formoterol treatment. These clinical findings correspond with the in vitro findings of flow-dependent fine particle mass from the Aerolizer, and corroborate the relationship between fine particle mass of aerosol and clinical effect. The results indicate a flow-dependent effect of formoterol dry powder inhaled from the Aerolizer, within the range of inspiratory flow rate obtainable by school-children. This questions its applicability in children with asthma.

Administration, Inhalation↗

Duration of action of formoterol and salbutamol dry-powder inhalation in prevention of exercise-induced asthma in children.

The aim of this study was to evaluate the effect and tolerability of formoterol 12 micrograms on exercise-induced asthma in children for 12 h as compared to the effect of salbutamol 400 micrograms and placebo. The drugs were inhaled as dry powder from a flow-dependent metered-dose inhaler (DP-MDI). Sixteen asthmatic children took part in a double-blind placebo-controlled within-patient single-centre trial. On each study day the patients were given one of the drugs or placebo in random order, and standardized exercise tests were performed after 3 and 12 h. At a pretrial test the children had demonstrated a median maximum percentage fall of 38% (range 22-79%) in forced expiratory volume in 1 s after exercise challenge. Formoterol showed a median percentage protection of 77% and 70% at 3 and 12 h postexercise, respectively, as compared to 46% and 13% with salbutamol. No side-effects were observed. Formoterol 12 micrograms administered as dry powder offers significantly better protection against exercise-induced asthma after 3 and 12 h as compared to salbutamol 400 micrograms and placebo.

Administration, Inhalation↗

[Is routine microscopy of tissue from induced abortions necessary?].

This study was performed in order to evaluate the importance of routine microscopy of tissue from legal abortions performed before the end of the 12th week of pregnancy. The tissues recovered from 580 abortions were examined carefully macroscopically before they were sent to microscopy. Five hundred and fifty-four samples (95.5%) were judged by macroscopic examination to contain the normal products of pregnancy. These all contained chorionic villi when examined histologically. Macroscopic examination was inconclusive in the remaining 26 samples (4.5%), 22 of these samples proved after all to contain chorionic villi when examined histologically. We conclude that histological examination of tissue from legal abortions is unnecessary in most cases if it is replaced by careful clinical examination of the sample, only to be followed by microscopy if the findings are uncertain.

Abortion, Induced↗