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Biomedical subjects

U Frey

Publications and source records attributed to U Frey.

At least 19 recordsLinked to original sources

Prospectively assessed incidence, severity, and determinants of respiratory symptoms in the first year of life.

Respiratory symptoms are common in infancy. Nevertheless, few prospective birth cohort studies have studied the epidemiology of respiratory symptoms in normal infants. The aim of this study was to prospectively obtain reliable data on incidence, severity, and determinants of common respiratory symptoms (including cough and wheeze) in normal infants and to determine factors associated with these symptoms. In a prospective population-based birth cohort, we assessed respiratory symptoms during the first year of life by weekly phone calls to the mothers. Poisson regression was used to examine the association between symptoms and various risk factors. In the first year of life, respiratory symptoms occurred in 181/195 infants (93%), more severe symptoms in 89 (46%). The average infant had respiratory symptoms for 4 weeks and 90% had symptoms for less than 12 weeks (range 0 to 23). Male sex, higher birth weight, maternal asthma, having older siblings and nursery care were associated with more, maternal hay fever with fewer respiratory symptoms. The association with prenatal maternal smoking decreased with time since birth. This study provides reliable data on the frequency of cough and wheeze during the first year of life in healthy infants; this may help in the interpretation of published hospital and community-based studies. The apparently reduced risk in children of mothers with hayfever but no asthma, and the decreasing effect of prenatal smoke exposure over time illustrate the complexity of respiratory pathology in the first year of life.

Asthma↗

ACE I/D but not AGT (-6)A/G polymorphism is a risk factor for mortality in ARDS.

The intrapulmonary renin-angiotensin system via tissue concentration of angiotensin II or bradykinin may have multiple effects on pulmonary pathophysiology. Therefore, it was investigated whether the presence of the D allele of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism or the A allele of angiotensinogen (AGT) promoter polymorphism (-6)A/G are independent risk factors for 30-day survival in acute respiratory distress syndrome (ARDS) patients. In a prospective study, adults (Germans of Caucasian ethnicity) with ARDS (n = 84) were recruited from the current authors' intensive care unit and genotyped for the ACE I/D and the AGT (-6)A/G polymorphisms, as were 200 healthy Caucasian controls. Mortality was increased in the ACE DD genotype compared with the I allele, and the ACE I/D polymorphism was an independent prognostic factor for 30-day survival. Patients with a homozygous DD genotype were at highest risk for death (hazard ratio 5.7; 95% confidence interval 1.7-19.2) compared with the II genotype. In contrast, the AGT (-6)A/G polymorphism was neither associated with an increased risk for development of ARDS nor with outcome. In patients with acute respiratory distress syndrome, the angiotensin-converting enzyme insertion/deletion polymorphism but not the angiotensinogen (-6)A/G promoter polymorphism is an independent risk factor with a pronounced effect on 30-day survival.

Adult↗

Single-chip microelectronic system to interface with living cells.

A high degree of connectivity and the coordinated electrical activity of neural cells or networks are believed to be the reason that the brain is capable of highly sophisticated information processing. Likewise, the effectiveness of an animal heart largely depends on such coordinated cell activity. To advance our understanding of these complex biological systems, high spatiotemporal-resolution techniques to monitor the cell electrical activity and an ideally seamless interaction between cells and recording devices are desired. Here we present a monolithic microsystem in complementary metal oxide semiconductor (CMOS) technology that provides bidirectional communication (stimulation and recording) between standard electronics technology and cultured electrogenic cells. The microchip can be directly used as a substrate for cell culturing, it features circuitry units per electrode for stimulation and immediate cell signal treatment, and it provides on-chip signal transformation as well as a digital interface so that a very fast, almost real-time interaction (2 ms loop time from event recognition to, e.g., a defined stimulation) is possible at remarkable signal quality. The corresponding spontaneous and stimulated electrical activity recordings with neuronal and cardiac cell cultures will be presented. The system can be used to, e.g., study the development of neural networks, reveal the effects of neuronal plasticity and study cellular or network activity in response to pharmacological treatments.

Action Potentials↗

Alterations of exhaled nitric oxide in pre-term infants with chronic lung disease.

Animal models suggest that reduced nitric oxide (NO) synthase activity results in lower values of exhaled NO (eNO) present at birth in those individuals who are going to develop chronic lung disease of infancy (CLDI). Online tidal eNO was measured in 39 unsedated pre-term infants with CLDI (mean gestational age (GA) 27.3 weeks) in comparison with 23 healthy pre-term (31.6 weeks) and 127 term infants (39.9 weeks) at 44 weeks post-conceptional age, thus after the main inflammatory response. NO output (NO output (V'(NO)) = eNO x flow) was calculated to account for tidal- flow-related changes. Sex, maternal atopic disease and environmental factors (smoking, caffeine) were controlled for. The mean eNO was not different (14.9 ppb in all groups) but V'(NO) was lower in CLDI compared with healthy term infants (0.52 versus 0.63 nL x s(-1)). Values for healthy pre-term infants were between these two groups (0.58 nL x s(-1)). Within all pre-term infants (n = 62), V'(NO) was reduced in infants with low GA, high clinical risk index for babies scores and longer duration of oxygen therapy but not associated with post-natal factors, such as ventilation or corticosteroid treatment. After accounting for flow, the lower nitric oxide output in premature infants with chronic lung disease of infancy is consistent with the hypothesis of nitric oxide metabolism being involved in chronic lung disease of infancy.

Breath Tests↗

Micro hot plate-based sensor array system for the detection of environmentally relevant gases.

A monolithic stand-alone gas sensor system is presented, which includes on a single chip an array of three metal oxide-coated micro hot plates with integrated MOS-transistor heaters, as well as a specifically designed digital system architecture. An octagonal-shaped micro hot plate design with MOS-transistor heaters has been adopted for the three gas sensors. The integrated circuitry includes a programmable digital temperature regulation, digital sensor readout units, and a standard serial interface. The programmable digital temperature controllers enable individual regulation of the micro hot plate temperatures in constant or dynamic mode. Nanocrystalline tin oxide thick films with different Pd dopings (undoped, 0.2 and 3 wt %) were used. Gas test measurements for environmentally relevant gases were carried out and evidenced detection limits of less than 1 ppm for carbon monoxide, or 100 ppm for methane, both at 40% relative humidity. Temperature modulation techniques were successfully applied for improved analyte discrimination.

Journal Article↗

New aspects of airway mechanics in pre-term infants.

High-frequency respiratory impedance data measured noninvasively by the high-speed interrupter technique (HIT), particularly the first antiresonance frequency (f(ar,1)), is related to airway wall mechanics. The aim of this study was to evaluate the feasibility and repeatability of HIT in unsedated pre-term infants, and to compare values of f(ar,1) from 18 pre-term (post-conceptional age 32-37 weeks, weight 1,730-2,910 g) and 18 full-term infants (42-47 weeks, 3,920-5,340 g). Among the pre-term infants, there was good short-term repeatability of f(ar,1) within a single sleep epoch (mean (sd) coefficient of variance: 8 (1.7)%), but 95% limits of agreement for repeated measures of f(ar,1) after 3-8 h were relatively wide (-41 Hz; 37 Hz). f(ar,1) was significantly lower in pre-term infants (199 versus 257 Hz), indicating that wave propagation characteristics in pre-term airways are different from those of full-term infants. The present authors suggest that this is consistent with developmental differences in airway wall structure and compliance, including the influence of the surrounding tissue. Since flow limitation is determined by wave propagation velocity and airway cross-sectional area, it was hypothesised that the physical ability of the airways to carry large flows is fundamentally different in pre-term than in full-term infants.

Feasibility Studies↗

[Acute asthma attacks in childhood].

The diagnosis of an acute asthmatic attack in a child is made on a clinical basis. The severity of the exacerbation can be assessed by physical examination and measurement of the transcutaneous oxygenation saturation. A blood gas analysis can be helpful in this assessment. A child with a severe asthma exacerbation should be promptly referred to an emergency department of a hospital. Oxygen should be given to keep the oxygen saturation above 92% and short-acting, selective beta-2 agonists should be administered. Beta-2 agonists can be delivered by intermittent nebulization, continuous nebulization or by metered dose inhaler (MDI) with a spacer They can also be given intravenously in patients who are unresponsive to escalating therapy. The early administration of systemic corticosteroids is essential for the management of acute asthma in children. When tolerated, systemic corticoseroids can be given orally but inhaled corticosteroids are not recommended. Oxygen delivery, beta-2 agonists and steroid therapy are the mainstay of emergency treatment. Hypovolemia should be corrected either intravenously or orally. Administration of multiple doses of ipratropium bromide has been shown to decrease the hospitalization rate in children and adolescents with severe asthma. Clinical response to initial treatment is the main criterion for hospital admission. Patients with failure to respond to treatment should be transferred to an intensive care unit. A critical aspect of management of the acute asthma attack in a child is the prevention of similar attacks in the future.

Acute Disease↗

Effect of sighs on breathing memory and dynamics in healthy infants.

Deep inspirations (sighs) play a significant role in altering lung mechanical and airway wall function; however, their role in respiratory control remains unclear. We examined whether sighs act via a resetting mechanism to improve control of the respiratory regulatory system. Effects of sighs on system variability, short- and long-range memory, and stability were assessed in 25 healthy full-term infants at 1 mo of age [mean 36 (range 28-57) days] during quiet sleep. Variability was examined using moving-window coefficient of variation, short-range memory using autocorrelation function, and long-range memory using detrended fluctuation analysis. Stability was examined by studying the behavior of the attractor with use of phase-space plots. Variability of tidal volume (VT) and minute ventilation (VE) increased during the initial 15 breaths after a sigh. Short-range memory of VT decreased during the 50 breaths preceding a sigh, becoming uncorrelated (random) during the 10-breath presigh window. Short-range memory increased after a sigh for the entire 50 breaths compared with the randomized data set and for 20 breaths compared with the presigh window. Similar, but shorter duration, changes were noted in VE. No change in long-range memory was seen after a sigh. Coefficient of variation and range of points located within a defined attractor segment increased after a sigh. Thus control of breathing in healthy infants shows long-range stability and improvement in short-range memory and variability after a sigh. These results add new evidence that the role of sighs is not purely mechanical.

Carbon Dioxide↗

Two-year periodicity of respiratory syncytial virus epidemics in Switzerland.

BACKGROUND: The annual respiratory syncytial virus (RSV) epidemics vary in time and severity. The aims of this study were (1) to describe the time-related pattern of RSV epidemics in Switzerland and (2) to deduce the most effective time period for administration of prophylactic measures to high-risk patients. PATIENTS AND METHODS: Descriptive study of (1) RSV hospitalizations between 1997 and 2001 at a pediatric hospital serving a population of 1 million and (2) of national RSV detection rates reported by diagnostic laboratories between 1988 and 1999. RESULTS: 497 RSV hospitalizations and 8,574 reported RSV detections occurring during four and 12 epidemics, respectively, were analyzed. There was fixed alternation of minor and major epidemics differing in the number of RSV infections (two to fourfold), evolution (median interval from onset to peak 13 weeks, range 4-13 weeks vs 8 weeks, range 7-10 weeks; p = 0.065) and median duration (26 weeks, range 24-29 weeks vs 19.5 weeks, range 18-21 weeks; p = 0.005). For minor epidemics it was estimated that a maximum of 85.6% (range, 79.4-86.6%) of annual RSV infections could be covered by a standard five-dose regimen of the monoclonal anti-RSV antibody palivizumab, if initiated in week 50. During major epidemics the most effective time of initiation would be week 43 (88.7%; range 81.9-94.6%). CONCLUSION: RSV epidemiology in Switzerland is characterized by fixed biannual variation. In the absence of active RSV surveillance, such periodicity is useful for scheduling RSV prophylaxis and for hospital resources management.

Disease Outbreaks↗

[Overview of standardised diagnostic instruments of dementia].

The symptoms of dementia refer to a decline in intellectual abilities and to an impairment of general and instrumental activities of daily living (ADL). Beside cognitive decline and loss of ADL's the diagnosis of dementia requires the documentation of changes in social adaptation, psychopathology and behaviour. There are a large number of scales used in the assessment of the various manifestations of the disease. Some scales focus on a particular aspect of the symptomatology, others prefer a comprehensive approach in the detection of dementia symptoms. We present a list of assessment procedures and scales which seem appropriate to detect different aspects of dementia and which are widely accepted in the scientific community. We describe these scales in detail including their methodology and source of informations, psychometric properties regarding validity and reliability as well as time taken to complete the scales. Our synopsis may serve as an orientation mark in the selection of adequate instruments for the assessment of different symptom domains during the process of diagnosis, the observation of the course of dementia and the efficacy of treatment interventions.

Activities of Daily Living↗

Reactive macrophage activation syndrome: a simple screening strategy and its potential in early treatment initiation.

QUESTIONS UNDER STUDY: starting treatment of reactive macrophage activation syndromes as early as possible (rMAS, haemophagocytic lymphohistiocytosis), e.g., with intravenous immunoglobulins (IVIG), seems to be essential for optimal outcome. However, there is no diagnostic gold standard which reliably indicates need for early treatment. We used a simple screening strategy consisting of serum ferritin measurements and/or morphological assessment of haemophagocytosis and compared the studied patient population with published series. METHODS: Retrospective analysis of clinical and laboratory data of 57 patients experiencing 60 episodes of rMAS. RESULTS: Screening by serum ferritin measurements and/or morphological assessment of haemophagocytosis of patients presenting with a systemic inflammatory response syndrome (SIRS) indicates that rMAS might be considerably more frequent than stated in the literature. Serum ferritin exceeded >10,000 microg/L in 91% rMAS episodes. Although the patient population studied was otherwise similar in most aspects to the published rMAS series, the fact that 40% of patients fulfilled the criteria for Still's disease (SD) as the disorder underlying rMAS is remarkable and questions the distinct nature of the two diseases. IVIG responders and non-responders did not differ regarding their initial characteristics with exception to the timepoint of IVIG administration, confirming the importance of early treatment initiation. Malignancy-associated rMAS however, has a poor prognosis and seems to be refractory to manipulation with IVIG in most instances, even when responding initially. CONCLUSIONS: rMAS has to be considered in patients with a SIRS- or SD-like clinical presentation. Hyperferritinaemia >or=10,000 microg/l seems to be a good marker for defining patients with or at risk for developing rMAS and should be completed with a morphological assessment of haemophagocytosis. The perception of acute SD and rMAS as two distinct entities has to be questioned at least in a subgroup of patients.

Adolescent↗

[Influence of treatment with acetyl-cholinesterase inhibitors on psychopathological symptoms in Alzheimer's disease].

The treatment of the cognitive deficits has been the major focus in patients with Alzheimer's disease (DAT) so far. Recently there is increasing interest in Behavioral and Psychological Symptoms of Dementia (BPSD), which can place much burden on DAT patients and their caregivers. With the introduction of Acetylcholinesterase Inhibitors (AChEI) of the second generation the therapeutic armament has been extended. The clinical evaluation of AChEI has found growing evidence that these compounds do not only improve cognitive abilities and activities of daily living (ADL), but also BPSD. The given data regarding the three AChEI available on the market allow the conclusion that there is a general improvement in BPSD. Beside these particularly positive effects on hallucinations, mood symptoms, aggressiveness, and agitation seem possible but need further clarification.

Activities of Daily Living↗

Role of lung function testing in the management of mechanically ventilated infants.

The mechanical characteristics of the ventilated lung can only be interpreted when the volume of the lung, the elastic properties, and the degree of airway obstruction have been accurately quantified by pulmonary function testing. More gentle ventilation strategies (permissive hypercapnia) are used, and the efficacy of mechanical ventilation can be verified in the intensive care unit. Pulmonary function testing brings new insights, awareness, and applications, but its limitations need to be taken into account when interpreting the acquired data.

Airway Resistance↗

Elevated nitrite in breath condensates of children with respiratory disease.

The aim of the study was to determine the differences in nitrite, in the exhaled breath condensates of healthy children and those children with asthma, cystic fibrosis (CF) and nonasthmatic, episodic cough. Breath condensates were obtained from 66 children (43 males:23 females, 3.1-16 yrs) and included 29 asthmatics, 12 clinically stable CF patients, 12 children with cough but not asthma and 13 healthy volunteers. The collected condensate was assayed colourimetrically using the Griess reaction to determine nitrite concentrations. Patients with CF (median: 5-95% percentiles; 2.02: 0.43-6.37 microM) or asthma (2.10: 0.63-5.45 microM) had significantly higher levels of nitrite compared to healthy subjects (0.41: 0.13-1.83 microM; p<0.05) or subjects with cough (0.75: 0.03-1.75 microM; p<0.05). Airway inflammation, as assessed by the nitrite in breath condensates, is present in children with asthma and cystic fibrosis, but not those children with nonasthmatic, episodic cough. Nitrite can be conveniently, cheaply and rapidly measured in breath condensates of children as young as 3 yrs of age, and may prove useful for the assessment of airway inflammation in children with respiratory disease.

Adolescent↗

Measurement of lung volume and ventilation distribution with an ultrasonic flow meter in healthy infants.

Small airway disease in infants is characterised by abnormal lung volume and uneven ventilation distribution. An inert tracer gas washin/washout technique using a pulsed ultrasonic flow meter is presented to measure functional residual capacity (FRC) and ventilation distribution in spontaneously breathing and unsedated infants. With a pulsed ultrasound sent through the main stream of the flow meter, flow, volume and MM of the breathing gas can be calculated. Sulphur hexafluoride was used as a tracer gas. In a mechanical lung model (volume range 53-188 mL) and in 12 healthy infants (aged 38.3+/-9.2 days; mean+/-SD) accuracy and reproducibility of the technique was assessed. Indices of ventilation distribution such as alveolar-based mean dilution number (AMDN) and pulmonary clearance delay (PCD) were calculated. Mean error of volume measurement in the lung model was 0.58% (coefficient of variance (CV) 1.3%). FRC was in the low predicted range for normal infants (18.0+/-2.0 mL x kg(-1)) and highly reproducible (5.5+/-1.7% intra-subject CV). AMDN was 1.63+/-0.15 and PCD was 52.9+/-11.1%. Measurement of functional residual capacity and ventilation distribution using a sulphur hexafluoride washin/washout and an ultrasonic flow meter proved to be highly accurate and reproducible in a lung model and in healthy, spontaneously breathing and unsedated infants.

Female↗

Age-related differences in perceived asthma control in childhood: guidelines and reality.

Current guidelines specify the goals of asthma treatment in children and propose a stepwise approach to achieve them. The authors sought to determine whether these goals were attained in children of different age groups in the community and to assess treatment in those with unsatisfactory asthma control. A cross-sectional postal questionnaire survey was performed in 1998 in all members of the major Swiss parents organisation for childhood asthma. With a response rate of 85%, data from 572 Swiss-German children aged 4-16 yrs with wheeze were analysed. Asthma control was excellent in 18% of the children, satisfactory (only episodic symptoms) in 33%, and unsatisfactory in 49% with disturbed sleep, restricted activities and school absences. When stratified by age, excellent or satisfactory control was attained by 66% of children aged 13-16 yrs, but only by 56%, 44%, and 38% of those aged 10-12, 7-9 and 4-6 yrs, respectively. Although the majority were followed-up by a doctor (95%) and were receiving beta2-agonists (82%) and inhaled corticosteroids (68%), intensity and duration of treatment were not sufficiently matched to asthma severity. In virtually all children there was scope to improve medical treatment, preventive measures and knowledge of asthma management, with very few if any children with therapy-resistant asthma. Even in children with poor asthma control, 89% of parents were satisfied with the results of treatment. The goals of asthma treatment were attained in one-half of the children, particularly in younger age groups. Although inhaler use was common, detailed assessment showed evidence for undertreatment, especially in the youngest age group, and insufficient adherence to preventive measures. Parental expectations of asthma control, which were lower than those outlined in guidelines, might be an important but underestimated factor in paediatric asthma management.

Administration, Inhalation↗

Why are infants prone to wheeze? Physiological aspects of wheezing disorders in infants.

Wheezing in infants is common and increasing in prevalence. Infants are particularly prone to wheezing due to developmental differences in airway mechanics compared to adults. These effects are enhanced in the presence of airway inflammation. Wheezing in infants is related to flow limitation which is a function of airway calibre and airway wall compliance. This review discusses the factors contributing to flow limitation and hence, wheezing. It tries to make the link between risk factors influencing airway structure, and thus function, with particular emphasis on the special physiological peculiarities of infants and lung growth. While in adults inflammation and remodelling alone may explain structural and functional changes in wheezing disorders, this reviews proposes a model emphasising that in infants inflammation, remodelling and airway development have to be considered as a continuously interacting system.

Algorithms↗