Biomedical subjects

L T Skovgaard

Publications and source records attributed to L T Skovgaard.

At least 19 recordsLinked to original sources

PubMed2005

Teenage girls and elderly women living in northern Europe have low winter vitamin D status.

OBJECTIVE: To determine the vitamin D status (serum 25-hydroxyvitamin D; S-25OHD) in adolescent girls and elderly community-dwelling women living in four countries of northern Europe and to explain differences in S-25OHD concentrations between and within the countries. DESIGN: A cross-sectional observational study conducted in a standardised way during February-March. S-25OHD was analysed by high-performance liquid chromatography. Vitamin D and calcium intake was calculated using a standardised food composition database. SETTING: Denmark, Finland, Ireland, and Poland. SUBJECTS: A total of 199 girls (mean (s.d.) age 12.6 (0.5) y) and 221 women (mean (s.d.) age 71.8 (1.4) y). RESULTS: The median (inter quartiles) concentration of S-25OHD was 29.4 (20.3, 38.3) nmol/l for the girls and 40.7 (28.0, 54.2) nmol/l for the women. S-25OHD below 25 nmol/l was found in 37% of the girls and 17% of the women, and S-25OHD below 50 nmol/l was found in 92% of the girls and 37% of the women. Positive significant determinants for S-25OHD in girls were use of vitamin D supplements, and in women sun habits, dietary vitamin D intake, use of vitamin D and calcium supplements. Body mass index and smoking were negative determinants in women. For women predictors could explain the differences between countries (P(country) = 0.09, R(2) = 0.39), but for girls the difference remained significant even after including predictors (P(country) = 0.03, R(2) = 0.15). CONCLUSION: Vitamin D status is low in northern Europe during winter. More than one-third of the adolescent girls have vitamin D status below 25 nmol/l and almost all are below 50 nmol/l. Two-thirds of the elderly community-dwelling women have vitamin D status below 50 nmol/l. Use of vitamin D supplements is a significant positive determinant for S-25OHD for both girls and women (P = 0.001). SPONSORSHIP: The European Fifth Framework Programme (Contract No. QLK1-CT-2000-00623).

Age Factors↗

PubMed2005

Short hard palate in prenatal trisomy 21.

OBJECTIVE: The aim of the present study was for the first time to examine on postmortal material the total midpalatal length of the hard palate and the length of its two components (the maxillary and palatine parts) in trisomy 21 fetuses, and to compare the results to normal standards. DESIGN: Material from 31 human fetuses with genetically verified trisomy 21 was studied. The fetuses were derived from legally induced or spontaneous abortions. Palates were, after sectioning, radiographed in lateral projection (Grenz Ray radiographic apparatus). Cephalometric measurements were performed with a digital caliper. Statistically, the length measurements for the two groups were compared, adjusting for crown rump length (CRL) through linear regression. At two specific ages (150 and 170 mm CRL), the length of the palatal components in trisomy 21 was compared to normal standards. RESULTS: For CRL 150 mm and CRL 170 mm it appears that all three palatal lengths, total length, maxillary length, and palatinal length are significantly shorter in fetuses with trisomy 21. CONCLUSION: The main conclusion of our study is that the total palatal length in prenatal trisomy 21 is shorter than normal and that this is due both to a shortness of the maxillary and the palatine components of the hard palate.

Cephalometry↗

PubMed2004

Volume adjustment of lung density by computed tomography scans in patients with emphysema.

PURPOSE: To determine how to adjust lung density measurements for the volume of the lung calculated from computed tomography (CT) scans in patients with emphysema. MATERIAL AND METHODS: Fifty patients with emphysema underwent 3 CT scans at 2-week intervals. The scans were analyzed with a software package that detected the lung in contiguous images and subsequently generated a histogram of the pixel attenuation values. The total lung volume (TLV), lung weight, percentile density (PD), and relative area of emphysema (RA) were calculated from this histogram. RA and PD are commonly applied measures of pulmonary emphysema derived from CT scans. These parameters are markedly influenced by changes in the level of inspiration. The variability of lung density due to within-subject variation in TLV was explored by plotting TLV against PD and RA. RESULTS: The coefficients for volume adjustment for PD were relatively stable over a wide range from the 10th to the 80th percentile, whereas for RA the coefficients showed large variability especially in the lower range, which is the most relevant for quantitation of pulmonary emphysema. CONCLUSION: Volume adjustment is mandatory in repeated CT densitometry and is more robust for PD than for RA. Therefore, PD seems more suitable for monitoring the progression of emphysema.

Absorptiometry, Photon↗

PubMed2004

Short-term reproducibility of computed tomography-based lung density measurements in alpha-1 antitrypsin deficiency and smokers with emphysema.

PURPOSE: To study the short-term reproducibility of lung density measurements by multi-slice computed tomography (CT) using three different radiation doses and three reconstruction algorithms. MATERIAL AND METHODS: Twenty-five patients with smoker's emphysema and 25 patients with alpha1-antitrypsin deficiency underwent 3 scans at 2-week intervals. Low-dose protocol was applied, and images were reconstructed with bone, detail, and soft algorithms. Total lung volume (TLV), 15th percentile density (PD-15), and relative area at -910 Hounsfield units (RA-910) were obtained from the images using Pulmo-CMS software. Reproducibility of PD-15 and RA-910 and the influence of radiation dose, reconstruction algorithm, and type of emphysema were then analysed. RESULTS: The overall coefficient of variation of volume adjusted PD-15 for all combinations of radiation dose and reconstruction algorithm was 3.7%. The overall standard deviation of volume-adjusted RA-910 was 1.7% (corresponding to a coefficient of variation of 6.8%). Radiation dose, reconstruction algorithm, and type of emphysema had no significant influence on the reproducibility of PD-15 and RA-910. However, bone algorithm and very low radiation dose result in overestimation of the extent of emphysema. CONCLUSION: Lung density measurement by CT is a sensitive marker for quantitating both subtypes of emphysema. A CT-protocol with radiation dose down to 16 mAs and soft or detail reconstruction algorithm is recommended.

Absorptiometry, Photon↗

PubMed2004

Thermodilution cardiac output--are three injections enough?

BACKGROUND: Bolus thermodilution cardiac output measurements have been a mainstay in clinical monitoring of critically ill patients for more than 30 years. Usually the results of an arbitrarily chosen number (1-6) of thermal indicator injections are averaged to increase the reliability of the measurement. The number of injections needed to achieve a given level of precision has, however, not previously been systematically investigated. METHODS AND RESULTS: In 80 hemodynamically stable patients cardiac output was determined as the average of eight injections of 10 ml of iced saline. From the 638 measurements we examined the relationship between the number of thermal indicator injections and the precision of the resulting cardiac output estimate. Furthermore, the association between the number of injections and the least detectable difference among two sets of measurements was established. CONCLUSION: The current study shows that one needs to average the results of four injections to be 95% confident that the result is within 5% of the 'true' cardiac output and that two series of four measurements have to differ by at least 7% before one can be sure (95%) that a change in cardiac function has taken place.

Adult↗

PubMed2004

The influence of jaw innervation on the dental maturation pattern in the mandible.

OBJECTIVES: To explore the relationship between mandibular dental maturation and the pattern of jaw innervation. SETTING AND SAMPLE POPULATION: The sample included 365 panoramic radiographs taken in the period 1965-1969 in a Danish municipality. DESIGN: For assessing dental maturity, the seven left mandibular teeth (M2, M1, P2, P1, C, I2, I1) were given a dental maturity score according to a method introduced by Demirjian. Spearman correlation coefficients between the maturity score of an index tooth (one of each teeth) and the maturity score of the 6 other teeth was calculated and illustrated. RESULTS: All the correlation coefficients were larger than 0.5 indicating a rather high level of association between the development of mandibular teeth in the same individual. Thus, associations between the pattern of dental maturation and jaw innervation were not obvious. CONCLUSION: When the correlation between the dental maturity stages was analysed, no significant relation was found between dental maturation and jaw innervation in the mandible. This is interesting considering the results presented in a recent study, which showed that the clinical observed tooth eruption was closely related to the pattern of jaw innervation. Those authors suggested that the factors influencing the eruption might be associated with jaw innervation. In our study, the stepwise dental maturation process, however, is not equally associated with jaw innervation.

Adolescent↗

PubMed2003

Pharmacokinetics and pharmacodynamics of mivacurium in patients phenotypically heterozygous for the usual and atypical plasma cholinesterase variants (UA).

BACKGROUND: Mivacurium is hydrolyzed by plasma cholinesterase (pChe). The purpose of this study was to evaluate the pharmacodynamics and the pharmacokinetics of the three isomers of mivacurium in patients phenotypically heterozygous for the usual and the atypical pChe variant (UA). METHODS: Thirty-two patients were included in a dose-response study, in which the patients received one of four doses of mivacurium. An additional bolus dose of mivacurium, to a total of 0.1 mg kg-1, was given followed by a continuous infusion adjusted to maintain 91-99% neuromuscular block. The times to different levels of recovery following the infusion were measured using mechanomyography and train-of-four (TOF) nerve stimulation. Twelve of the patients with an estimated duration of anaesthesia of more than 90 min were (randomly) selected for the pharmacokinetic part of the study. Venous samples were taken for determination of the three isomers of mivacurium. These results were compared with results from a previous study in phenotypically normal patients (UU). RESULTS: The estimated ED50 and ED95 were 24 and 69 microg kg-1, respectively. The median (range) infusion rate was 3.7 microg kg-1 min-1 (1.2-2.9) and the time to a TOF ratio of 0.7 was 29.8 min (16.1-44.8). The median clearances of the cis-cis, cis-trans and trans-trans isomers were 3.7, 29 and 28 ml kg-1 min-1, respectively. The elimination half-lives of the isomers were 45, 6.7 and 6.3 min, respectively. CONCLUSION: In patients heterozygous for the usual and the atypical variant (UA), the potency of mivacurium is higher, the infusion requirements lower and the rate of spontaneous recovery prolonged, compared with phenotypically normal patients. The clearances of the active isomers are significantly lower and the elimination half-lives longer in heterozygous patients than in phenotypically normal patients (UU). The pharmacokinetics of the inactive cis-cis isomer was not affected.

Adolescent↗

PubMed2002

Postoperative muscle paralysis after rocuronium: less residual block when acceleromyography is used.

BACKGROUND: Residual muscle paralysis after anesthesia is common after pancuronium, but less common following the intermediate-acting drugs vecuronium and atracurium. Therefore, many anesthetists do not monitor neuromuscular function when using an intermediate-acting agent. The purpose of this prospective, randomised and double-blind study was to establish the incidence and degree of postoperative residual block following the use of rocuronium in patients not monitored with a nerve stimulator, and to compare it with results obtained in patients monitored using acceleromyography (AMG). METHODS: During propofol/opioid anesthesia, 120 adult patients were randomised to two groups, one monitored with AMG, the other using only clinical criteria without a nerve stimulator. Postoperatively, TOF-ratio was measured with mechanomyography; a TOF-ratio < 0.80 indicated residual muscle paralysis. RESULTS: Residual muscle paralysis was found in 10 patients in the group without neuromuscular monitoring (16.7%) (95% confidence interval, 12-21%) and in two patients in the AMG-monitored group (3%) (95% CI, 0-8%); (P = 0.029, Fisher's exact test). Time from end of surgery to tracheal extubation was significantly longer in the AMG-monitored group (12.5 min) than in the group not monitored with AMG (10 min). CONCLUSION: Clinical evaluation of recovery of neuromuscular function does not exclude significant residual paralysis following the intermediate-acting muscle relaxant rocuronium, but the problem of residual block can be minimized by use of AMG.

Adolescent↗

PubMed2002

Pharmacokinetics and pharmacodynamics of mivacurium in young adult and elderly patients.

BACKGROUND: Mivacurium is hydrolyzed by plasma cholinesterase, and is therefore less dependent on liver metabolism and renal elimination than other neuromuscular blocking drugs. This might favor the use of mivacurium in elderly patients. The purpose of this study was to compare the pharmacodynamics and the pharmacokinetics of the three isomers of mivacurium and their metabolites in young adult and elderly patients. METHODS: Sixty-four patients were included in a dose-response study, in which 32 young adults and 32 elderly patients received one of four doses of mivacurium. An additional bolus dose of mivacurium to a total of 0.1 mg/kg was given followed by a continuous infusion adjusted to maintain a 91-99% neuromuscular block. The times to maximum block and different levels of recovery were measured using mechanomyography and train-of-four (TOF) nerve stimulation. Thirty-two patients were randomly selected for the pharmacokinetic study. Venous samples were taken for determination of the three mivacurium isomers and the metabolites. RESULTS: The estimated ED95 were 0.053 and 0.061 mg/kg in young adults and elderly patients, respectively (NS). The median infusion rate did not differ, but duration to a TOF ratio of 0.7 was significantly longer in elderly patients than in young adult patients (21.0 vs. 16.5 min). No statistically significant difference between the age groups in clearance and elimination half-life of the isomers was seen. The half-lives of the metabolites were significantly prolonged in the elderly patients. CONCLUSION: There were no significant differences in the potency or infusion requirements between the adult and elderly patients, but the rate of recovery was significantly, though only moderately prolonged, in the elderly patients. No significant difference in clearance was seen but the elimination half-lives of the metabolites was longer in the elderly patients.

Adolescent↗

PubMed2001

[Research in Danish departments of anesthesiology at the turn of the century. A bibliometric analysis].

INTRODUCTION: This investigation was based on the surmise that the scientific activity in the specialty of anaesthesiology and intensive care medicine in Denmark is declining. MATERIAL AND METHODS: A quantitative and qualitative analysis of the development in Danish anaesthesiological research during the seven-year period of 1992-1998 was performed with bibliometrical methods and a count of the PhD and doctoral theses produced by Danish anaesthesiologists during that period. RESULTS: In the period investigated, a total of 906 scientific articles were published, of which 749 (83%) originated from university hospitals. Total production decreased by 15% between the two-year periods of 1992-1993 and 1997-1998, whereas the output from university hospitals alone decreased by 10%. The number of scientific publications per anaesthesiologist decreased by 34%, corresponding to 6.7% per year. The quality of the research published, as examined by the cumulative and average impact, showed a slight increase. The number of PhD and doctoral theses per year showed no change. DISCUSSION: Research activity in Danish anaesthesiology is declining, and the specialty seems to be losing scientific ground, both nationally and internationally.

Academic Dissertations as Topic↗

PubMed2001

Seasonal and biological variation of urinary epinephrine, norepinephrine, and cortisol in healthy women.

BACKGROUND: There is a significant circadian and seasonal periodicity in various endocrine functions. The present study describes the within-day and seasonal fluctuation for urinary catecholamines and cortisol and estimates the within- (CV(i)) and between-subject (CV(g)) coefficients of variation for healthy women undertaking their routine work. In addition, index of individuality (I(i)) and power calculations were derived. METHODS: Eleven healthy females undertaking their routine life-style at work participated in the study. Each subject collected six samples during 24 h 15 days over a year, giving a total number of 990 samples. Using a random effect analysis of variance, we estimated CV(g) and total within-subject variation (CV(ti)), i.e. combined within-subject and analytical variation, from logarithmically transformed data. Analytical variation was subtracted from CV(ti) to give CV(i). CV(i) was estimated from samples collected monthly during 1 year (CV(iy)), weekly during 1 month (CV(im)), and six to eight times/day (CV(id)). RESULTS: A seasonal variation was demonstrated for excretion of epinephrine, norepinephrine, and cortisol standardized with creatinine. Concentrations of urinary epinephrine were higher during June and July compared to the rest of the year, whereas concentrations of urinary cortisol were higher during December and January compared to the rest of the year. Excretion of norepinephrine was lower during working hours and higher during hours off work for June and July compared to the rest of the year. There was a high within- and between-subject variation, which could not be explained by menstrual cycle, behavioral, emotional, or cognitive stress reactions. CONCLUSIONS: Despite high biological variation a reasonably low sample size, e.g. 10-50 individuals, is adequate for practical applicability, i.e. studying differences above 150%. The present study recommends to include the sampling time in the statistical evaluation of data and to be aware of the changes in diurnal variations over seasons. When single measurements are to be evaluated, reference intervals are recommended.

Adult↗

PubMed2001

Bi-iliac distance and iliac bone position compared to the vertebral column in normal fetal development.

Prenatal standards of bi-iliac width were not found in the literature based on autopsy investigations, nor was the caudo-cranial position of the ilia compared to the vertebral column. The first purpose of the present study was to establish normal standard values for the bi-iliac distance in fetal life, the second to evaluate the level of the iliac bones proportional to the ossified vertebral column. Whole body radiographs in antero-posterior projections from 98 human fetuses (36 female and 44 male fetuses, as well as 18 fetuses on which the sex had not been determined) were analyzed in the study. The fetuses derived from spontaneous or induced abortions and they were radiographed as part of the required autopsy procedure. The crown-rump-length (CRL) of the fetuses varied from 32 to 245 mm. The outer and inner bi-iliac distance was measured from the radiographs with a digital Helios slide caliper. The caudo-cranial position of the iliac bones was evaluated. The present study shows that in normal fetal development there is a continuous linear enlargement of the pelvic region in the transverse and vertical planes. The upper iliac contour stays at the level of the first sacral vertebral body, whereas the lower iliac line moves caudally. Significant differences between male and female fetuses were not found. The value of the present study is that the results can be used as reference standards in prenatal pathology.

Embryonic and Fetal Development↗

PubMed2001

A method to reduce the number of measured parameters when using isokinetic muscle strength as a clinical indicator in rheumatoid arthritis patients.

The aim of the study was to present a method enabling a reduction of the number of measurements when quantifying isokinetic muscle strength (IMS), and to describe an expression for IMS which is independent of measuring conditions. IMS is a measure of muscle strength used to categorise patients and to assess changes over time. IMS measurements involve one or several measures of peak torque at different chosen angular velocities. Comparisons between studies are difficult and an expression of IMS independent of measuring conditions is needed. Thirty-six women with rheumatoid arthritis were followed for 1 year. IMS was measured on five occasions on both knees at seven angular velocities, giving 10 sets of peak-torque data for each patient. The log[peak-torque]-angular-velocity diagram showed a linear relationship. From this, the peak-torque value at the chosen angular velocity of 30 degrees/s (IMS30) was estimated for each test and the uncertainties involved were quantified. IMS30 is a reliable parameter when comparing effort between knees, visits and patients, and may be based on three sets of data only. IMS may be expressed by a single value, IMS30, representing the fitted line in a log[peak-torque]-angular-velocity diagram. The regression line may be fitted by three or more angular velocities. In principle, IMS30 is independent of the chosen angular velocity, which makes it possible to use an estimated value as IMS30 to compare results, studies and centres in between.

Arthritis, Rheumatoid↗

PubMed2001

The assessment of postoperative cognitive function.

Postoperative cognitive function (POCD) has been subject to extensive research. In the literature, large differences are apparent in methodology such as the test batteries, the interval between sessions, the endpoints to be analysed, statistical methods, and how neuropsychological deficits are defined. Traditionally, intelligence tests or tests developed for clinical neuropsychology have been used. The tests for detecting POCD should be based on well-described sensitivity and suitability in relation to surgical patients. In tests using scores, floor/ceiling effects may compromise the evaluation if the tests are either too easy or to difficult. Uncontrolled testing facilities and change of test personnel may affect the test performance. Practice effects are pronounced in neuropsychological tests but have generally been ignored. The use of a suitable normative population is essential to allow correction for practice effects and variability between sessions. Missing follow-up may severely compromise valid conclusions since subjects unable or unwilling to be examined are particularly prone to suffer from POCD. In the statistical analysis of the test results, the evaluation should be based on differences between pre- and postoperative performance. Parametric statistical tests are not relevant unless the appropriate Gaussian distributions are present, perhaps after transformation of data. The definition of cognitive dysfunction should be restrictive and the criteria should be fulfilled in only a small proportion of volunteers. In the literature, these requirements often have not been fulfilled. This precludes a reasonable estimation of the incidence of POCD and the conclusions of comparative studies should be interpreted with great caution. In this review article, we present a number of recommendations for the design and execution of studies within this area. In addition, the critical reader may use these recommendations in the evaluation of the literature.

Affect↗

PubMed2001

Onset and duration of action of rocuronium--from tracheal intubation, through intense block to complete recovery.

BACKGROUND: The primary objective of this study was to establish the relation between the post tetanic count (PTC) and the time to reappearance of the first response (T1) in train-of-four (TOF) nerve stimulation following rocuronium 0.6 mg/kg, 0.9 mg/kg, and 1.2 mg/kg. The secondary objective was to evaluate the intubation conditions after 1 min. METHODS: One hundred and eight patients were randomised to one of three doses of rocuronium: 0.6, 0.9 or 1.2 mg/kg. Tracheal intubation was performed at 60 s by a blinded investigator. During propofol, fentanyl, midazolam anaesthesia the neuromuscular block was monitored by mechanography using TOF stimulation every 12 s. At 6 min intervals, a tetanic stimulation (50 Hz) was applied for 5 s preceded and followed by a 30 s period of 1 Hz stimulation until the reappearance of T1. RESULTS: There was a significant difference in recovery following the high dose and the two lower doses. The relation between time (min) to reappearance of T1 (t) and PTC can be expressed as follows: t(0.6 and 0.9 mg/kg)(min)=18.8-6.46 PTC and t(1.2 mg/kg)(min)=26.1-9.12 PCT. T1 was seen at a mean PTC level of 8 or 9 in all three groups. The intubation conditions were graded as excellent or good in all patients except in two patients following the 0.6 mg/kg dose of rocuronium. CONCLUSION: The PTC method can be used to predict the time to first response to TOF nerve stimulation during intense rocuronium induced neuromuscular blockade. The relation between PTC and the time to T1 was prolonged after 1.2 mg/kg compared with 0.6 mg/kg and 0.9 mg/kg. No further improvement in intubation conditions at 60 s was evident by increasing the rocuronium dose from 0.9 mg/kg to 1.2 mg/kg.

Adolescent↗

PubMed2000

Effects of Pluronic F-68 on Tetrahymena cells: protection against chemical and physical stress and prolongation of survival under toxic conditions.

The effects of the non-ionic surfactant Pluronic F-68 (0.01% w/v) on Tetrahymena cells have been studied. A marked protection against chemical and physical stress was observed. The chemical stress effects were studied in cells suspended in buffer (starvation) or in buffers with added ingredients from a chemically defined medium (Ca2+, Mg2+, Na+, K+, trace metal ions). The physical stress was due to mechanical stress or hyperthermia. The data show that Pluronic: (a) prolongs the survival of low concentration cell suspensions during starvation; (b) prevents the cell death caused by low concentrations of Ca2+ (70 microM); (c) prolongs the survival of cells exposed to higher ion concentrations (10 mM Ca2+, or Na+ or K+); (d) postpones the death caused by trace metal ions like Zn2+, Fe3+ and, Cu2+; (e) protects cells from the death caused by shearing forces; and (f) prolongs the survival of cells exposed to hyperthermia (43 degrees C). The cellular survival is increased at reduced temperatures (e.g. 4 degrees C instead of 36 degrees C) and at increased cellular concentrations (e.g. 100 cells ml(-1) instead of 25 or 10 cells ml(-1)). There is no effect of pre-incubation with Pluronic. The protective effect of Pluronic towards Tetrahymena is observed for concentrations in the range from 0.001 to 0.1% w/v.

Animals↗

PubMed2000

Pharmacokinetic studies of neuromuscular blocking agents: good clinical research practice (GCRP).

In September 1997, an international consensus conference on standardization of studies of neuromuscular blocking agents was held in Copenhagen, Denmark. Based on the conference, a set of guidelines for good clinical research practice (GCRP) in pharmacokinetic studies of neuromuscular blocking agents is presented. Guidelines include: design of the study; relevant patient groups to investigate; test drug administration, sampling and analysis; pharmacokinetic analysis; pharmacokinetic/pharmacodynamic modeling; population pharmacokinetics; statistics; and presentation of pharmacokinetic data. The guidelines are intended to aid those working in this research area; it is hoped that they will assist researchers, editors of scientific papers, and pharmaceutical companies in improving the quality of pharmacokinetic studies.

Body Temperature↗

PubMed2000

Rapid development in vitro and in vivo of resistance to ceftazidime in biofilm-growing Pseudomonas aeruginosa due to chromosomal beta-lactamase.

The aim of this study was to examine the development of resistance of biofilm-growing P. aeruginosa during treatment with ceftazidime. Biofilms were established in vitro using a modified Robbins device (MRD) and in vivo in the rat model of chronic lung infection. Three P. aeruginosa strains isolated from the lungs of cystic fibrosis (CF) patients (MICceftazidime-basal/induced beta-lactamase activity: PAO 579= 0.8 mg/l-19/550 milliunits, 19676A=50 mg/l-38/957 milliunits, 17107B=100 mg/l-504/947 milliunits) were studied. After 1 or 2 weeks of continuous or intermittent (4 h/day) administration of ceftazidime to biofilms established in MDR, a statistically significant development of resistance to ceftazidime in PAO 579 or 19676A bacterial populations occurred. When ceftazidime was administered 4 h/day (200 mg/l) for 2 weeks, the frequency of resistant 19676A having MIC>25 mg/l was 4.4 10(-1) compared to 6.0-10(-5) in the control biofilm. The same trend was observed after continuous administration of ceftazidime. MICceftazidime of the more resistant variants was increased 500-fold for PAO 579 and 8-fold for 19676A, and the specific basal beta-lactamase activities from 19 to 1,400 units for PAO 579 and from 38 to 10,000 units for 19676A. Chronic P. aeruginosa lung infection was established with alginate-embedded PAO 579, 19676A or 17107B in 146 Lewis rats which were treated with ceftazidime 4 g/kg intraperitoneally twice a day for 1 week. A statistically significant development of resistance was observed for all three strains. The MICceftazidime of the more resistant variants was increased 15-fold for PAO 579, 8-fold for 19676A, and 4-fold for 17107B, and the specific basal 3-lactamase activity from 19 to 100 units for PAO 579, from 38 to 1,300 units for 19676A, and from 500 to 1,300 units for 17107B. It was shown that, during treatment with ceftazidime, biofilm-growing P. aeruginosa had the capacity to develop resistance due to the production of chromosomal beta-lactamase.

Animals↗