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Biomedical subjects

P Gustafsson

Publications and source records attributed to P Gustafsson.

At least 19 recordsLinked to original sources
PubMed2005

Do all dry powder inhalers show the same pharmaceutical performance?

Important measures of pharmaceutical performance of dry powder inhalers include total emitted dose (TED, the quantity of drug emitted from the device when used at a fixed flow rate, typically 60 l/min or the flow rate achieved at a pressure drop of 4 kPa) and fine particle mass (FPM, the quantity of drug with small particles, typically with an aerodynamic diameter of less than 5 microns emitted from the device at a fixed flow rate). There is a wide range of dry powder inhalers available. The complexity of design decisions means that dry powder inhalers are very diverse, with identical designs unlikely. It is not surprising therefore that evidence from in vitro studies shows considerable variation in pharmaceutical performance of dry powder inhalers. Although neither TED nor FPM can accurately predict in vivo performance, it may be expected that highly variable or inhalation flow sensitive in vitro behaviour will be reflected in variable performance when used by patients.

Administration, Inhalation↗
PubMed2005

Can patients use all dry powder inhalers equally well?

If patients are unable to use their inhaler, drug delivery may be unsatisfactory and the patients may fail to benefit from the prescribed medication. It is important to consider whether patients can use all dry powder inhalers equally well. Changing a patient from a dry powder inhaler used well to one that the patient is unable to operate effectively could compromise asthma control. The many marketed dry powder inhalers reflect differences in design decisions that could affect lung deposition. Studies using different dry powder inhalers have confirmed that different lung deposition patterns are observed. Furthermore, there may be considerable individual variability in lung deposition. Differences in lung deposition patterns could have clinical effects. Studies may show similar clinical effectiveness with two inhalers, because most products are used at the plateau phase of the dose-response curve, although there may be differences in the adverse event profile. The ideal inhaler does not yet exist. Different dry powder inhalers show some but not all features of the ideal inhaler; hence, patients may prefer some aspects of one inhaler while favouring a different inhaler for other features. The individual balance of features will govern the overall preference for one inhaler over others. The method for operation of dry powder inhalers varies. Ease of use is seen as an important consideration when selecting an inhaler device, which should be evaluated in real-life studies using unselected patient populations. In conclusion, the evidence suggests that patients cannot use all dry powder inhalers equally well.

Administration, Inhalation↗
PubMed2004

Multiple breath inert gas washout as a measure of ventilation distribution in children with cystic fibrosis.

BACKGROUND: Multiple breath inert gas washout (MBW) has been suggested as a tool for detecting early cystic fibrosis (CF) lung disease. A study was undertaken to compare the relative sensitivity of MBW and spirometry for detecting abnormal lung function in school age children with CF and to compare MBW results obtained from healthy children in the UK with those recently reported from Sweden. METHODS: Forced expiratory volume in 1 second (FEV1) and maximal expiratory flow when 25% of forced vital capacity remains to be expired (MEF25) were compared with the lung clearance index (LCI) derived from sulphur hexafluoride MBW in 22 children with CF aged 6-16 years and in 33 healthy controls. RESULTS: LCI was higher in children with CF than in healthy controls (mean difference 5.1 (95% CI of difference 4.1 to 6.1) and FEV1 and MEF25 z-scores were lower (mean difference -2.3 (95% CI -2.9 to -1.7) and -1.8 (95% CI -2.4 to -1.3), respectively; p<0.001 for all). There was a significant negative correlation between LCI and FEV1 (r2 = 0.62) and MEF25 (r2 = 0.46). However, while normal (> or =-1.96 z-scores) FEV1 and MEF25 results were seen in 11 (50%) and 12 (53%) children with CF, respectively, all but one of these children had an abnormally increased LCI. LCI was repeatable in both groups (within subject CV for three measurements 6% for CF and 5% for healthy children). In healthy subjects LCI was independent of age and virtually identical in the British and Swedish children (mean difference 0.1 (95% CI -0.1 to 0.4), p = 0.38) CONCLUSIONS: MBW is reproducible between laboratories, generates normal ranges which are constant over childhood, and is more frequently abnormal than spirometry in children with CF.

Adolescent↗
PubMed2002

Clinical equivalence between salbutamol hydrofluoroalkane pMDI and salbutamol Turbuhaler at the same cumulative microgram doses in paediatric patients.

This study aimed to demonstrate equivalent efficacy and safety between salbutamol delivered via the HFA134a pMDI (Hydrofluoroalkane 134a pressurised Metered Dose Inhaler) and the Turbuhaler dry powder inhaler in asthmatic children. This was a randomised, double-blind, double-dummy, placebo-controlled, crossover study in 10 asthmatic children aged 6-15 years who demonstrated at least 10% reversibility of FEV1 after inhaling 400 microg of salbutamol. On 5 single study days subjects received either placebo or cumulative doses of 100, 200, 400 and 800 microg of salbutamol at 30 minute intervals. Both devices were placebo on one study day while each device was active on two study days. FEV1 was measured before and 20 minutes after each dose. Heart rate was measured before spirometry. Mean FEV1 and heart rate at each time point and the area under the dose response time curve (AUC) were analysed using ANOVA. FEV1 increased similarly after cumulative doses of salbutamol on each of the study days, irrespective of device. Mean treatment difference in AUC was 0.01 L. min (95%CI -0.05 to 0.08 L). Heart did not differ at any dose. It is concluded that salbutamol delivery from a HFA pMDI and Turbuhaler is equivalenton a microgram basis in asthmatic children for efficacy and safety.

Adolescent↗
PubMed2001

The properties of the chlorophyll a/b-binding proteins Lhca2 and Lhca3 studied in vivo using antisense inhibition.

The specific functions of the light-harvesting proteins Lhca2 and Lhca3 were studied in Arabidopsis ecotype Colombia antisense plants in which the proteins were individually repressed. The antisense effect was specific in each plant, but levels of Lhca proteins other than the targeted products were also affected. The contents of Lhca1 and Lhca4 were unaffected, but Lhca3 (in Lhca2-repressed plants) was almost completely depleted, and Lhca2 decreased to about 30% of wild-type levels in Lhca3-repressed plants. This suggests that the Lhca2 and Lhca3 proteins are in physical contact with each other and that they require each other for stability. Photosystem I fluorescence at 730 nm is thought to emanate from pigments bound to Lhca1 and Lhca4. However, fluorescence emission and excitation spectra suggest that Lhca2 and Lhca3, which fluoresce in vitro at 680 nm, also could contribute to far-red fluorescence in vivo. Spectral forms with absorption maxima at 695 and 715 nm, apparently with emission maxima at 702 and 735 nm, respectively, might be associated with Lhca2 and Lhca3.

Antisense Elements (Genetics)↗
PubMed2001

The bias flow nitrogen washout technique for measuring the functional residual capacity in infants. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing.

The functional residual capacity (FRC) is the most commonly measured static lung volume in infants. It is important for interpreting volume-dependent pulmonary mechanics, e.g. airway resistance, and defining normal lung growth. The bias flow nitrogen washout technique is widely used for measuring FRC because the dead space and circuit resistance are low, making it suitable for small or sick infants. Moreover, data acquisition and calculation are easily programmed for a personal computer. The aim of this paper is to provide recommendations pertaining to equipment requirements, study procedures and reporting of data for functional residual capacity measurements. While measuring the functional residual capacity is regarded as physiologically and clinically important, the accuracy of the measurement is undoubtedly equally important. Hence, the paper also emphasizes factors influencing the accuracy of functional residual capacity measurements independent of equipment requirements. These recommendations represent the "State of the Art" in 2000.

Clinical Protocols↗
PubMed2001

CP43', the isiA gene product, functions as an excitation energy dissipator in the cyanobacterium Synechococcus sp. PCC 7942.

Under conditions of iron deficiency certain cyanobacteria induce a chlorophyll (Chl)-binding protein, CP43', which is encoded by the isiA gene. We have previously suggested that CP43' functions as a nonradiative dissipator of light energy. To further substantiate its functional role an isiA overexpression construct was introduced into the genome of a cyanobacterium Synechococcus sp. PCC 7942 (giving isiAoe cells). The presence of functional CP43' in isiAoe cells was confirmed by Western blot as well as by the presence of a characteristic blueshift of the red Chl a absorption peak and a notable increase in the 77 K fluorescence peak at 685 nm. Compared to wild-type cells isiAoe cells, with induced CP43', had both smaller functional antenna size and decreased yields of room temperature Chl fluorescence at various light irradiances. These observations strongly suggest that isiAoe cells, with induced CP43', have an increased capacity for dissipating light energy as heat. In agreement with this hypothesis isiAoe cells were also more resistant to photoinhibition of photosynthesis than wild-type cells. Based on these results we have further strengthened the hypothesis that CP43' functions as a nonradiative dissipator of light energy, thus protecting photosystem II from excessive excitation under iron-deficient conditions.

Bacterial Proteins↗
PubMed2000

Decreased expression of two key enzymes in the sucrose biosynthesis pathway, cytosolic fructose-1,6-bisphosphatase and sucrose phosphate synthase, has remarkably different consequences for photosynthetic carbon metabolism in transgenic Arabidopsis thaliana.

Photosynthetic carbon metabolism was investigated in antisense Arabidopsis lines with decreased expression of sucrose phosphate synthase (SPS) and cytosolic fructose-1,6-bisphosphatase (cFBPase). In the light, triose phosphates are exported from the chloroplast and converted to sucrose via cFBPase and SPS. At night, starch is degraded to glucose, exported and converted to sucrose via SPS. cFBPase therefore lies upstream and SPS downstream of the point at which the pathways for sucrose synthesis in the day and night converge. Decreased cFBPase expression led to inhibition of sucrose synthesis; accumulation of phosphorylated intermediates; Pi-limitation of photosynthesis; and stimulation of starch synthesis. The starch was degraded to maintain higher levels of sugars and a higher rate of sucrose export during the night. This resembles the response in other species when expression of enzymes in the upper part of the sucrose biosynthesis pathway is reduced. Decreased expression of SPS inhibited sucrose synthesis, but phosphorylated intermediates did not accumulate and carbon partitioning was not redirected towards starch. Sugar levels and sucrose export was decreased during the night as well as during the day. Although ribulose-1,5-bisphosphate regeneration and photosynthesis were inhibited, the PGA/triose-P ratio remained low and the ATP/ADP ratio high, showing that photosynthesis was not limited by the rate at which Pi was recycled during end-product synthesis. Two novel responses counteracted the decrease in SPS expression and explain why phosphorylated intermediates did not accumulate, and why allocation was not altered in the antisense SPS lines. Firstly, a threefold decrease of PPi and a shift of the UDP-glucose/hexose phosphate ratio favoured sucrose synthesis and prevented the accumulation of phosphorylated intermediates. Secondly, there was no increase of AGPase activity relative to cFBPase activity, which would prevent a shift in carbon allocation towards starch synthesis. These responses are presumably triggered when sucrose synthesis is decreased in the night, as well as by day.

Arabidopsis↗
PubMed2000

Associations between cerebral blood-flow measured by single photon emission computed tomography (SPECT), electro-encephalogram (EEG), behaviour symptoms, cognition and neurological soft signs in children with attention-deficit hyperactivity disorder (ADHD).

Twenty-eight children with attention-deficit hyperactivity disorder (ADHD) were examined with SPECT (single photon emission computed tomography). Seven of the children had abnormal distribution of the regional cerebral blood-flow (rCBF) on visual evaluation and 10 had abnormal EEG findings. The only clinical finding that differentiated the group with normal from abnormal rCBF was behaviour symptom load. A factor analysis of the rCBF in different regions of interest yielded one factor with low rCBF in the temporal and cerebellar regions and high rCBF in the subcortical and thalamic regions, which was significantly associated with the degree of motor impairment and results on a cognitive test (WISC). Another factor consisting of high rCBF in frontal and parietal regions had a significant negative correlation with the degree of behaviour symptoms. There was a negative correlation between the rCBF in the right frontal regions and the degree of behaviour symptoms. The number of minor physical anomalies (MPA) was negatively correlated to the rCBF in the frontal lobes bilaterally. These results suggest that there may be at least two functional disturbances in ADHD, one specific neurodevelopmentally determined disturbance of the frontal lobes, especially of the right hemisphere, related to behaviour deviance, and another disturbance of the integration of the temporal lobes, the cerebellum and subcortical structures, related to motor planning and aspects of cognition.

Attention Deficit Disorder with Hyperactivity↗