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Biomedical subjects

B Klug

Publications and source records attributed to B Klug.

At least 19 recordsLinked to original sources
PubMed2000

Complex segregation analysis of families ascertained through Gilles de la Tourette syndrome.

Although family and twin studies suggest that genetic factors are involved in the etiology of Tourette syndrome and other related tic disorders, further evidence is needed to demonstrate that the familial transmission is consistent with known genetic factors. We performed a complex segregation analysis that allowed for a variable age of onset of Gilles de la Tourette, other tic disorders and obsessive compulsive phenotype information on 108 extended families, each ascertained through one Tourette proband by using regressive models that are able to incorporate additional explanatory variables and major gene effects. A special version of the S.A.G.E. program, REGTLhunt, was used to explore the likelihood surface of all examined models. Results indicated that the pattern of Tourette and other related tic disorders in our data sample is not consistent with Mendelian inheritance even after modelling explanatory variables such as obsessive compulsive symptomatology.

Adolescent↗
PubMed2000

Relative incompetence of european rabbits for Lyme disease spirochaetes.

To determine whether rabbits may serve as reservoir hosts for Lyme disease spirochaetes in Europe, we compared their competence as hosts for Borrelia afzelii, one of the most prevalent European spirochaetal variants, with that of the Mongolian jird. To infect rabbits or jirds, at least 3 nymphal or adult Ixodes ricinus ticks infected with spirochaetes fed to repletion on each animal. Whereas jirds readily acquired tick-borne Lyme disease spirochaetes and subsequently infected vector ticks, rabbits exposed to tick-borne spirochaetes rarely became infectious to ticks. Only the rabbit that was infectious to ticks developed an antibody response. To the extent that I. ricinus ticks feed on European rabbits, these mammals may be zooprophylactic by diverting vector ticks from more suitable reservoir competent hosts.

Animals↗
PubMed2000

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↗
PubMed1999

The fluctuating pattern of various genome types of respiratory syncytial virus in Copenhagen and some other locations in Denmark.

A semi-nested RT-PCR method based on a region of the F and G glycoprotein genes was established, allowing the simultaneous detection and differentiation of group A and group B isolates of respiratory syncytial virus (RSV). The PCR products were subjected to digestion with restriction endonucleases to further differentiate the isolates. Using, in addition, previously reported studies the prevalence of various genome types in the Copenhagen region over a period of 6 years was established. Furthermore, the prevalence of genome types was determined in a distant region in Denmark during the winters of 1996/97 and 1997/98, and in yet another distant region during the winter of 1997/98. It was shown that the different regions in Denmark to a large extent share the same pool of genome types of RSV. Yet, while the fluctuating patterns of the two groups and various genome types were almost identical at different hospitals in the Copenhagen region, they varied between the different regions. This suggests that epidemics in local communities primarily rely on region-specific herd immunity parameters and emerge from strains endemically circulating in these local communities. Group B strains in Copenhagen showed an overall predominance, being predominant in three of the six epidemic seasons studied, and of almost equal predominance in one season.

Child↗
PubMed1999

Lung function and short-term outcome in young asthmatic children.

The aims of this study were to investigate lung function in 2-5-yr-old stable asthmatic children consecutively referred from general practitioners and to analyse the outcome on the basis of their requirement for antiasthmatic treatment and symptoms after 1.6-4.5 yrs. Lung function was measured in 110 children with a mean+/-SD age of 3.8+/-1.0 yrs using the interruptor technique (resistance assessed using the interruptor technique (Rint)), whole body plethysmography (specific airway resistance (sRaw) and respiratory resistance (Rrs,5)and reactance at 5 Hz (Xrs,5) using the impulse oscillation technique. Rint, sRaw, Xrs,5 and Rrs,5 were suggestive of impaired lung function in 44%, 14%, 11% and 7.5% of the children, respectively, with a predominance of children aged 2-3 yrs. Sixty-five per cent were treated with inhaled steroids, and 35% were treated only with beta2-agonists as needed; lung function was not significantly different between these two groups. Outcome after 2.9+/-0.7 yrs was not significantly different between children with Rint measurements above and those children with Rint measurements within the reference range at enrolment. Of these children, 58 and 59% were currently on antiasthmatic treatment, and 40% and 49% had current symptoms, respectively. Impairment of lung function may be a common finding in stable young asthmatic children, but apparently this is not a risk factor for persistence of asthmatic symptoms.

Anti-Asthmatic Agents↗
PubMed1998

Specific airway resistance, interrupter resistance, and respiratory impedance in healthy children aged 2-7 years.

We report data on respiratory function in healthy children aged 2-7 years in whom we measured respiratory resistance by the interrupter technique (Rint); total respiratory impedance (Zrs), respiratory resistance (Rrs), and reactance (Xrs) by the impulse oscillation technique; and specific airway resistance (sRaw) by a modified procedure method in the whole body plethysmograph. Measurements were attempted in 151 children and were successfully obtained in 121 children with a mean (SD) age of 5.3 (1.5) years; no measurements were possible in 30 children (mean age 3 (0.9) years). The repeatability of measurements was independent of the age of the subjects, and the within-subject coefficient of variation was 11.1%, 8.1%, 10.8%, and 10.2% for sRaw, Rint, Zrs, and Rrs at 5 Hz (Rrs5), respectively. All lung function indices were linearly related to age, height, and weight. A significant negative correlation with age, height, and weight was found for Rint, Zrs, and Rrs5. Xrs5 was positively correlated to age and body size. The mean values of Rint, Rrs5, Xrs5, and Zrs in children younger and older than 5 years were 1.04, 1.38, -0.5, and 1.48 kPa x L(-1) x s and 0.9, 1.18, -0.37, and 1.23 kPa x L(-1) x s, respectively. sRaw showed no significant correlation with body size or age and the mean sRaw in children younger and older than 5 years was 1.09 and 1.13 kPa x s, respectively. None of the indices of respiratory function differed between boys and girls. Xrs and Rrs exhibited a significant frequency dependence in the range of 5-35 Hz. The techniques applied in this study require minimal cooperation and allow measurement of lung function in 80% of our population of awake young children. Further studies are needed to evaluate the potentials of the presently established reference values for clinical and epidemiological purposes.

Airway Resistance↗
PubMed1998

Severity of respiratory syncytial virus disease related to type and genotype of virus and to cytokine values in nasopharyngeal secretions.

BACKGROUND: Investigations concerning the severity of respiratory syncytial virus (RSV) disease as related to (1) RSV type and genotype determined respectively by PCR and restriction enzyme analysis and (2) interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) values in samples of nasopharyngeal secretion (NPS) have not been previously reported. METHODS: We prospectively studied 105 RSV infections in the lower respiratory tract of infants and young children admitted to a pediatric department in Copenhagen during three winter seasons, 1993, 1994 and 1995. RSV strains were typed and genotyped, respectively, by PCR and nucleic acid restriction analysis and correlated to the severity of the disease. The ratio IL-6:TNF-alpha, determined from IL-6- and TNF-alpha values in samples of NPS, was related to the severity of the disease. Concentrations of IL-6 and of TNF-alpha were determined in serum samples taken during 5 weeks after the onset of illness. RESULTS: Type B infections produced more severe disease than did type A infections, as assessed on the length of the hospital stay, use of respiratory support and the presence of an infiltrate on a chest radiograph. This difference was age-related. It was observed in infants 0 to 5 months old, but not in older age groups. Type B genotype B1122 produced more severe disease than type A genotype A2311 in infants 0 to 11 months old. Increased serum concentrations of IL-6 and TNF-alpha were detected in samples taken 1 to 2 days after the onset of illness. Whereas TNF-alpha serum concentrations remained high, IL-6 serum concentrations decreased during the following 3 to 4 weeks. The IL-6:TNF-alpha ratio in samples of NPS was related to the severity of the disease. A high ratio was related to a low severity. CONCLUSIONS: The severity of disease in patients admitted with acute RSV infections can be correlated to the RSV type as determined by PCR, to the RSV genotype as determined by nucleic acid restriction analysis and to the ratio IL-6:TNF-alpha in NPS.

Child, Preschool↗
PubMed1998

Diversity of European Lyme disease spirochetes at the southern margin of their range.

We determined whether the genospecies diversity of Lyme disease spirochetes in vector ticks questing on a subtropical island is as broad as that in Central Europe. Although spirochetes infected < 1% of the ticks sampled on Madeira Island, these infections included all three genospecies implicated in human disease. Therefore, spirochetal diversity is as great at the southern margin as it is in the center of this pathogen's range.

Animals↗
PubMed1998

Failure of Ixodes ticks to inherit Borrelia afzelii infection.

To define conditions promoting inherited infection by Lyme disease spirochetes in Ixodes ticks, we variously infected ticks with Borrelia afzelii and examined their progenies by dark-field microscopy, immunofluorescence, PCR, and serial passage. No episode of inherited infection was evident, regardless of instar or gender infected or frequency of exposure. We suggest that these spirochetes rarely, if ever, are inherited by vector ticks.

Animals↗
PubMed1998

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↗
PubMed1998

Fine particle mass from the Diskus inhaler and Turbuhaler inhaler in children with asthma.

The study aimed to investigate dose consistency and particle distribution from the dry powder inhalers Diskus and Turbuhaler. Full profiles of inhalation pressure versus time were recorded in 18 4 yr old and 18 8 yr old asthmatic children through Diskus and Turbuhaler inhalers. These data were used in an inhalation profile simulator to assess drug delivery from both a Diskus inhaler and a Turbuhaler inhaler, and in particular to assess the proportion of drug emitted in the coarse (>4.7 microm) and fine (<4.7 microm) particle size range from each type of inhaler. The inhalation profile more accurately represents the changes in flow rate over time through the device than the constant flow rate usually applied with an impactor alone. The aerosol cloud was released before the peak inspiratory effort had been achieved and accordingly the early part and not the peak of the inspiratory performance is a determinant of the quality of the aerosol. The mean (SD) amount of drug in large particles (>4.7 microm), fine particles (<4.7 microm) and very fine particles (<2.1 microm) in percentage of label claim from the Fluticasone Diskus was 72 (5), 15 (2) and 2 (1) from the 4 yr old children and 71 (3), 18 (2) and 2 (1) from the 8 yr old children, respectively. Similar particle fractions from the Budesonide Turbuhaler were 35 (9), 21 (10) and 7 (5) from 4 yr old children and 30 (7), 32 (9) and 12 (6) from 8 yr old children. In conclusion, the Diskus inhaler provides an improved dose consistency through the varying age groups and inspiratory flow performances when compared to the Turbuhaler in terms of the proportion of the dose emitted at each particle size. This improvement is at the expense of a low fine particle mass and a high proportion of coarse particles from the Diskus as compared with the Turbuhaler.

Androstadienes↗
PubMed1997

Repeatability of methacholine challenges in 2- to 4-year-old children with asthma, using a new technique for quantitative delivery of aerosol.

To determine the repeatability of bronchial responsiveness in awake young children, two methacholine challenge tests were performed on separate days in 16 children with stable asthma (mean age, 3 3/4 years). Methacholine was administered using a new method for quantitative delivery of aerosol that eliminates the effect of dilution of the aerosol by entrainment of air and enables quantitative delivery of aerosol according to body weight. Respiratory function was monitored by measurement of respiratory resistance by the interrupter technique (Rint), respiratory resistance and reactance at 5 Hz (Rrs5, Xrs5) by the impulse oscillation technique, transcutaneous measurements of oxygen (PtcO2), and specific airway resistance (sRaw). Repeatability was evaluated by determining the provocative dose that caused a defined percentage of change relative to baseline (PD%: Rint PD30, Rrs5 PD30, Xrs5 PD80, PtcO2 PD10, and sRaw PD80. Repeatability was estimated from the difference between the PD% obtained at the time of the two tests. Using the numeric value of these differences, the repeatability of Xrs5 PD60, PtcO2 PD10, and sRaw PD50 was [mean (SD)]: [0.8 (0.5)] [0.5 (0.4)] and [0.7 (0.6)] doubling doses, respectively. Rint PD30 and Rrs5 PD30 proved to be less reproducible: [1.2 (1)] and [1.6 (0.9)] doubling doses, respectively. The new method of aerosol delivery offers a means of standardizing the bronchoconstrictor stimulus, and the results show that estimates of bronchial responsiveness in young children can be obtained reproducibly within one doubling dose of methacholine.

Aerosols↗
PubMed1997

Restriction pattern variability of respiratory syncytial virus during three consecutive epidemics in Denmark.

A PCR-based assay was used to distinguish between respiratory syncytial virus (RSV) group A and B in order to analyze their prevalence in Denmark in three consecutive epidemics during the winters of 1992/93, 1993/94 and 1994/95. A total of 96 RSV strains isolated from hospitalized children were examined, showing alternation of group prevalence. Furthermore, the genetic variability of the RSV isolates was illustrated by restriction enzyme analysis of PCR products originating from a part of the F and G proteins that has been reported to be highly variable. We found that, in general, different genome types predominated each year, some types being present in consecutive epidemics, indicating a contribution of strains circulating unattended between outbreak seasons, while others seemed to disappear or became undetectable, being replaced by emerging types. Some of the genome types found seemed related to strains isolated up to more than two decades ago in other parts of the world. This indicates that the temporal fluctuation in predominance of genome types presumably caused by selective pressure exerted by host immunity is due to the favoring of strains from a pool of globally circulating, genetically relatively stable genome types, rather than a molecular evolution in strains induced or directed by immunoselective pressure.

Animals↗
PubMed1997

Measurement of the specific airway resistance by plethysmography in young children accompanied by an adult.

The purpose of this study was to evaluate a procedure for measurement of specific airway resistance (sRaw) by whole body plethysmography in young awake children accompanied by an adult. sRaw was measured by a single-step procedure, omitting the measurement of the thoracic gas volume. The frequency dependency of sRaw was investigated and the accuracy of simulating body temperature, atmospheric pressure and saturation with water vapour (BTPS) conditions by electronic compensation was assessed. One hundred and thirty one children with asthma were studied. In 57 children (mean (SD) age 5.6 (1.8) yrs) who performed measurements with and without an accompanying adult, the mean value of sRaw was 1.45 (0.36) and 1.44 (0.38) kPa x s, respectively, with a mean difference of 0.008 (0.152) kPa x s, and mean within-subject coefficients of variations (CV) of 8% and 10%, respectively. In 52 children (mean age 3.3 (0.8) yrs), for whom measurements made only in the presence of an accompanying adult, the CV was 8.5%. No measurements could be obtained in 22 children (17%) (mean age 2.8 (0.5) yrs). Measurements exhibited a significant frequency dependency, and electronic BTPS compensation substantially overestimated SRaw. In conclusion, the use of electronic compensation for simulating body temperature, atmospheric pressure and saturation with water vapour introduces a bias that affects the accuracy of the estimate of specific airway resistance. Nevertheless, plethysmographic measurements with and without an accompanying adult yielded comparable and equally repeatable estimates of specific airway resistance. The single-step plethysmographic procedure with an accompanying adult is a clinically useful method for evaluating airway function in children too young to perform plethysmographic measurements alone.

Adult↗
PubMed1997

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↗