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Biomedical subjects

Christian Koch

Publications and source records attributed to Christian Koch.

At least 19 recordsLinked to original sources

Investigation of spatial distribution of sound field parameters in ultrasound cleaning baths under the influence of cavitation.

Ultrasound cleaning baths fitting the full range from micromechanical components up to large machine parts, are regularly used in industry and in the lab. Despite the large number of applications, generally approved principles and objective criteria for parameter settings which allow an efficient operation are non-existent. The empirical selections of the running parameters often impede an optimization in terms of produce and reproducibility. One proposal for an objective description of the processes is the characterization of the sound field in the cleaning bath, which causes cavities, and subsequently, the cleaning process. Sound field measurements in the appropriate frequency range from 20kHz up to more then 1MHz incorporate a number of problems, such as large sensors disturbing the sound field, a lack of accuracy and the risk of being destroyed by cavitation bubbles. Measurement systems based on optical fiber tips and piezo-electrical hydrophones will be presented, which fulfil the accuracy requirements and withstand ultrasound fields with high power and cavitation. The spatial distribution of sound field parameters such as positive and negative peak pressure, amplitudes of fundamentals, harmonics and sub-harmonics as well as the energy density and spectral density in several frequency ranges are determined in experiments. Finally, the determined field parameters are related to the cavitation effects by means of photometric analysis of perforated aluminium foil. Perforations as well as intentions are analyzed and quantified from scanner images of the exposed foil samples using special image processing software. The experiments indicate clear differences in the structure of the sound fields and the spectral properties between the several types of cleaning baths, transducer arrangements and excitations.

Detergents↗

Early rise of anti-pseudomonas antibodies and a mucoid phenotype of pseudomonas aeruginosa are risk factors for development of chronic lung infection--a case control study.

P. aeruginosa is the most significant pathogen in CF lung disease. Chronic infection is preceded by a period of intermittent colonization. Early aggressive antimicrobial treatment at initial detection of P. aeruginosa in lower respiratory tract (LRT) secretions can prevent transition to chronic infection in approximately 80% of the patients, while the rest progress to chronic infection in spite of treatment. To analyze risk factors for development of chronic infection, a cohort of 89 CF patients free of chronic infection at the study period start was followed for 10 years. 28 of the patients (study group) developed chronic infection in spite of early treatment and 28 age-matched patients who did not (controls) were included in the analysis. During the 3 years period prior to onset of chronic infection, P. aeruginosa-positive cultures were more frequent in the study group than in the controls (2.2 vs. 0.5 per year, p<0.0001). Growth of mucoid strains of P. aeruginosa was more frequent in study group than in controls (11.5% vs. 0%, p<0.0001). Most important, specific anti-pseudomonal IgG serum antibodies were significantly higher in the study group than in controls (0.98 Elisa Units vs. 0.53, p=0.04) already 3 years prior to onset of chronic infection and increased 0.44 EU pr year in the study group but remained at the initial level in the control group (p<0.005). Occurrence of Aspergillus-positive cultures were significantly more frequent in the study group than in controls (p=0.01). The strongest risk factor for development of chronic P. aeruginosa infection was increasing levels of specific anti-pseudomonal antibodies, specifically of IgG1 and IgG4 subclass and total anti-Pseudomonas IgG, 3 years prior to onset of chronic infection, with odds ratio (OR) 8.9, 7.7 and 7.4, respectively (p<0.005), and growth of mucoid P. aeruginosa strains with OR of 7.4, p=0.006). Occurrence of Aspergillus was also a risk factor for developing chronic P. aeruginosa infection with the OR of 4.7 (p=0.008).

Adolescent↗

Effect of aerosolized rhDNase (Pulmozyme) on pulmonary colonization in patients with cystic fibrosis.

BACKGROUND: Aerosolized recombinant human deoxyribonuclease (rhDNase I (Pulmozyme)) has previously been shown to increase pulmonary function and reduce exacerbations of respiratory symptoms in cystic fibrosis (CF) patients with moderate to severe reduction in pulmonary function. AIM: To analyse whether aerosolized Pulmozyme could reduce the number of bacterial infections in the lower respiratory airways of CF patients without chronic pulmonary infection. METHODS: Patients were randomized either to aerosolized Pulmozyme 2(1/2) mg once daily or to no rhDNase treatment. The study period was 1 y, and the study was blinded for the Department of Clinical Microbiology. RESULTS: Overall, the number of positive cultures was significantly higher in the untreated group (82%) compared with the treated group (72%) (p<0.05). The most striking difference was found for Staphylococcus aureus, with a prevalence of 30% in the untreated group compared with 16% in the treated group (chi2 test, p<0.0001). Pulmonary function (FEV1) in the treated group showed a significant increase of 7.3% compared to 0.9% in the untreated group (p<0.05). CONCLUSION: Long-term DNase treatment was beneficial to CF patients without chronic lower respiratory tract infection, leading to reduced demand for antibiotics and to improved lung function.

Administration, Inhalation↗

Infusion pump delivers over-dosage of propofol as a result of missing syringe support.

We describe the malfunction of a common drug infusion pump. The syringe saddle was missing and allowed the syringe barrel to contact the pump case, which decreased the outward displacement of the syringe clamp. Then, the infusion pump falsely detected a smaller syringe size and consequently delivered an increased infusion rate and overdose of propofol to the patient. More commonly, an incorrectly mounted syringe may increase the outward displacement of the syringe clamp so that the infusion pump falsely detects a larger syringe size, with resultant less than expected infusion rate.

Drug Delivery Systems↗

Prevalence of allergic bronchopulmonary aspergillosis in cystic fibrosis in an area with a high frequency of atopy.

BACKGROUND: Lower airway colonisation with Aspergillus fumigatus and the complicating hypersensitivity reaction allergic bronchopulmonary aspergillosis (ABPA) is well recognised in patients with cystic fibrosis (CF). There is a wide range in reported prevalence of ABPA in CF. Differences in predisposing factors such as atopy and climatic humidity, but also differences in reporting may in part explain this observation. In the Australian population there is a high frequency of atopy and the climate is relatively humid. PATIENTS AND METHODS: Children and adolescents with CF (n = 277) from the CF Clinic, Children's Hospital at Westmead, Sydney, Australia were included in a retrospectively conducted study of Aspergillus colonisation and ABPA (1998-2003). RESULTS: The prevalence of Aspergillus colonised patients increased significantly from 7.4% in 1998 to 18.8% in 2002. No seasonal variation in initial positive Aspergillus culture or in humidity was observed. A total of 13 patients (4.7%) were diagnosed with ABPA over the study period, with a significant increase in prevalence from 0.3% in 1998 to 4.0% in 2002. In addition, the criteria used for reporting ABPA in the study population were in agreement with the recently published diagnostic criteria for ABPA in CF. CONCLUSIONS: In spite of a high frequency of atopy and a relatively humid climate in the Sydney area, Aspergillus colonisation and ABPA in CF patients was not disproportionate. Moreover, criteria for reporting of ABPA in this setting was not different from that in the Northern Hemisphere.

Adolescent↗

Long-term azitromycin treatment of cystic fibrosis patients with chronic Pseudomonas aeruginosa infection; an observational cohort study.

BACKGROUND: In cystic fibrosis (CF), chronic endobronchial infection with Pseudomonas aeruginosa is a serious complication. Macrolides can increase lung function and weight in patients, and reduce exacerbations. METHODS: In 2001, we introduced long-term, low-dose azithromycin (AZ) treatment as an integral part of our routine treatment of these patients. Our study is an observational cohort study of all CF patients with chronic P. aeruginosa infection in our CF center comparing clinical parameters of the patients 12 months prior to treatment with the same values during 12 months of treatment. RESULTS: 45 patients (27 men, median age 29 years) completed 1-year treatment. Median weight increased from 63.1 kg in the pre-treatment period to 63.9 kg during treatment (p=0.01). Median slope of decline in lung function increased from pre-treatment FEV1 -4.1% and FVC -3.0% to +0.8% (p<0.001) and +1.6% (p=0.01), respectively. 90% of sputum samples contained mucoid P. aeruginosa before treatment, decreasing to 81% during treatment (p=0.003). Median CRP decreased from 6.2 mmol/l to 5.8 mmol/l (ns). CONCLUSION: Long-term, low-dose AZ treatment in adult CF patients with chronic P. aeruginosa infection is safe and reduces the decline in lung function, increases weight, and reduces the percentage of mucoid strains of P. aeruginosa in sputum samples.

Adolescent↗

Measurement of spatial cross sections of ultrasound pressure fields by optical scanning means.

The measurement of spatial cross sections of ultrasound pressure fields is an essential element of exposimetry of ultrasonic medical equipment. An optical technique is presented that allows the two-dimensional (2-D) determination of ultrasound pressure using an optical multilayer hydrophone in which a laser beam with suitable wavelength is partially reflected from a dielectric optical multilayer system. By detecting the change in reflectivity of the multilayer coating induced by the incident ultrasound, the pressure time waveform can be determined. A 2-D data acquisition covering an area of at least 15 mm x 5 mm was realized by two complementary approaches. A serial detection scheme was set up by scanning the sensing point across the area of interest by a micromechanically engineered scanning mirror and acquiring pressure time waveforms sequentially and pointwise. This allows the measurement of repeating ultrasonic waveforms with a spatial resolution of better than 70 microm and a minimal detectable pressure of 50 kPa (bandwidth: 50 MHz) in a few seconds. In an alternative approach exploiting the parallel processing capabilities of a charge-coupled devices (CCD) camera chip, the probe was strobe-illuminated by a large-diameter collimated beam of a pulsed laser diode. The 2-D pressure distribution at a particular moment was derived from captured reflectivity distributions with a spatial resolution of 75 microm. By successive delaying of the laser pulse with respect to the ultrasound pulse, the complete 2-D pulse waveform was acquired with high spatial resolution. Measurement results on ultrasound fields from plane and focusing transducers are presented and compared to simulation results. Individual advantages and drawbacks of both approaches are discussed. A combined setup merging both detection schemes into a single device was developed and represents a milestone on the way toward constructing an optical ultrasound measuring camera.

Journal Article↗

Serum concentrations of GM-CSF and G-CSF correlate with the Th1/Th2 cytokine response in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection.

The inflammation in cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa lung infection is dominated by polymorphonuclear neutrophils (PMNs). There seems to be a relationship between the PMN-dominated inflammation, pronounced antibody production and a Th2-dominated response. Apart from mobilizing monocytes and PMNs from the bone marrow, GM-CSF, G-CSF and IL-3 select subsets of dendritic cells, which subsequently induce distinct Th responses. Therefore, the present study examines the correlation between the mobilizing cytokines in serum and the Th responses. The IFN-gamma and IL-4 production by peripheral blood mononuclear cells, and the concentrations of GM-CSF and G-CSF in serum as well as lung function, were determined in 37 CF patients with and 6 CF patients without chronic P. aeruginosa lung infection. The GM-CSF/G-CSF ratio correlated both with the IFN-gamma production and good lung function. In addition, an inverse correlation between IL-3 and IFN-gamma was observed. The results indicate involvement of endogenous GM-CSF, G-CSF and IL-3 in the skewed Th response in CF, and change to a Th1-dominated response might be achieved with GM-CSF treatment.

Adolescent↗

Serial lung function and responsiveness in cystic fibrosis during early childhood.

In a 4-year prospective study, we evaluated specific airway resistance (sRaw) by whole-body plethysmography, respiratory resistance by the interrupter technique, and respiratory resistance and reactance at 5 Hz by the impulse oscillation technique combined with measurement of responsiveness to bronchodilators and cold air in 30 children (mean [range] age 5.7 [2 to 8] years) with cystic fibrosis (CF). Spirometry was done at school age. Mean sRaw was consistently abnormal: the mean z score (SD) was 2.52 (2.02) (p < 0.001) at the start and was unchanged 36 months later at 2.74 (2.02). Mean z score (SD) for FEV(1) at first satisfactory measurement, at a mean age (range) of 6.1 (4.9-7.5) years was -1.2 (1.2) and was further reduced to -1.85 (1.2) 4 years from inclusion at a mean age (range) of 9.9 (6.8-12) years. Neither respiratory resistance by the interrupter technique nor the impulse oscillation technique demonstrated consistent abnormal levels. Patients with CF as a group did not differ from healthy subjects in responsiveness to bronchodilators and cold air. sRaw may be a useful tool in CF during early childhood. Reduced lung function was documented from consistently abnormal levels of sRaw and FEV1 during the study. Bronchodilator responsiveness and response to cold air challenge were normal.

Airway Resistance↗

Antibody response to Pseudomonas aeruginosa in cystic fibrosis patients: a marker of therapeutic success?--A 30-year cohort study of survival in Danish CF patients after onset of chronic P. aeruginosa lung infection.

We studied the effects of increasingly intensive treatment regimens on anti-pseudomonal antibody response and survival in five successive cohorts of a total of 157 Danish cystic fibrosis patients after they had acquired chronic P. aeruginosa lung infection. The time periods were 1971-1975 (N = 21), 1976-1980 (N = 64), 1981-1986 (N = 27), 1987-1993 (N = 26), and 1994-2000 (N = 19). During this 30-year period, we introduced elective 2-week courses of chemotherapy every third month in all chronically infected patients, early aggressive treatment with inhalation of colistin and oral ciprofloxacin for 3 months whenever P. aeruginosa was cultured in sputum from noncolonized patients, and inhalation of recombinant human dornase alfa. There was a significant correlation between the calendar year when chronic P. aeruginosa infection was acquired and the subsequent increase in the level of precipitins (P < 0.00001). The median number of precipitins increased by 5 per year in the oldest calendar year cohort, and 1 per year in the youngest. The median age of onset of chronic P. aeruginosa increased from 9.3 years from 1981-1986 to 13.8 years from 1987-2000. Survival after acquisition of chronic P. aeruginosa lung infection improved with time (P = 0.008). Our study shows that CF patients who are treated intensively have lower antibody responses and longer survival after acquisition of chronic P. aeruginosa lung infection.

Anti-Bacterial Agents↗

Epidemic spread of Pandoraea apista, a new pathogen causing severe lung disease in cystic fibrosis patients.

We show that Pandoraea apista must be added to the increasing list of pathogens capable of causing chronic lung infection in cystic fibrosis (CF) patients. It is most likely that this strain of P. apista was transmissible among patients with CF, leading to spread of infection from the index patient to 5 other patients exposed during participation in winter camps and/or hospitalization. All patients developed chronic infection with high levels of antibodies, and 4 patients had a downhill course of lung disease. P. apista must therefore be considered a new and sometimes important pathogen for CF patients. Cohort isolation prevented further spread of P. apista in our CF center.

Adult↗

Determination of temperature elevation in tissue during the application of the harmonic scalpel.

The temperature elevation in tissue during the application of the harmonic scalpel (UltraCision, operating frequency 55 kHz; Ethicon Endo-Surgery, Norderstedt, Germany) was determined using thermocouples of a specific design. In experiments with and without perfusion, two different scalpel blades were applied to three different kinds of pig tissue (lung parenchyma, tongue, parotid gland) in various configurations. Temperature elevations by more than 40 degrees C were found at 1 mm distance from the blade, whereas at distances of more than 5 mm, perfusion removed the heat very efficiently. The differences in the heating potential of the two blades were small and, at a distance of 2 mm, the temperature elevation did not exceed 6 degrees C at all. In histological investigations, the damaged area between blade and parenchyma was determined. No morphologic indications of thermal damage were found at a distance of more than 2 mm. It is concluded that, during application of the harmonic scalpel, a safety margin of 3 mm from sensitive structures should be kept.

Animals↗

Patient cohorting and infection control.

Patients with cystic fibrosis (CF) have an abnormal propensity for recurrent and chronic infections of the lower respiratory tract (LRT), and the most common cause of a shortened lifespan is chronic infection with Pseudomonas aeruginosa. A few other gram-negative organisms, primarily Burkholderia cepacia complex have, however, emerged as serious pathogens capable of establishing chronic LRT infection. Details of these and other CF pathogens can be found in the article by Dr. John LiPuma, Burkholderia and Emerging Pathogens in Cystic Fibrosis, in this issue. Chronically infected patients constitute a major microbial reservoir from which noninfected patients can be infected with both P. aeruginosa and B. cepacia complex by direct patient-to-patient transmission, and possibly also by exposure to contaminated environments. Other more rare pathogens such as Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and nontuberculous mycobacteria (NTM) appear less capable of causing patient-to-patient transmission. Both the physical proximity and the duration of exposure of noninfected patients to patients chronically infected with P. aeruginosa and B. cepacia complex are important determinants of the risk of cross-infection. Cohorting of patients according to presence or absence of specific pathogens coupled with conventional hygienic precautions can, however, lead to a decrease in incidence and prevalence of chronic infections with these two species, wherefore patient cohorting is now an integral component of infection control in patients with CF.

Journal Article↗

Amplitude and phase calibration of hydrophones by heterodyne and time-gated time-delay spectrometry.

Two methods for the amplitude and phase calibration of hydrophones based on time-delay spectrometry are presented: a time-gating technique and heterodyne frequency conversion that allows the phase-locked (i.e., coherent detection) of hydrophone signals. Amplitude and phase of the hydrophone sensitivity are obtained in the frequency range 1-20 MHz. In addition, to show the broad-band capabilities of the methods, amplitude values are measured between 4 and 50 MHz.

Letter↗

Mannose-binding lectin (MBL) therapy in an MBL-deficient patient with severe cystic fibrosis lung disease.

Deficiency of mannose-binding lectin has been shown to be a risk factor for cystic fibrosis (CF) patients. We, therefore, decided to treat a patient with CF, mannose-binding lectin deficiency, severe bronchopulmonary Pseudomonas aeruginosa infection, and rapid deterioration of lung function with purified mannose-binding lectin in an attempt to ameliorate the course of the lung disease. The mannose-binding lectin used originated from pooled human donor plasma and was given as an intravenous infusion twice a week for a period of 3 months. The patients's clinical condition was stabilized during the treatment period, but was not improved. No adverse events were observed. However, the lung function assessed as percent forced expiratory volume in 1 sec (FEV1%) and percent forced vital capacirt (FVC%) correlated significantly with the mannose-binding serum lectin levels (rho=+0.68, P=0.008, and rho=+0.73, P=0.004). Additionally, an inverse correlation with the acute phase-reactant C-reactive protein and the proinflammatory cytokine IL-6 was observed (rho=-0.49, P=0.007 and rho=-0.41, P=0.04, respectively). The results emphasize the importance of mannose-binding lectin as a secondary disease modifier in CF. Moreover, purified mannose-binding lectin can safely be administered to chronically ill patients, and may be a potential treatment in CF and other diseases in which mannose-binding lectin deficiency plays a pathophysiological role.

Adult↗

Early infection and progression of cystic fibrosis lung disease.

Chronic Pseudomonas aeruginosa infection is the major limitation in overall survival of patients with cystic fibrosis, and elective bronchoscopy shows that infection with this organism starts at a very early age. Early infection with nonmucoid P. aeruginosa gradually develops into chronic infection, characterized by the presence of microcolonies of alginate-producing (mucoid) P. aeruginosa in the bronchial tree. Chronic infection cannot be cured, but aggressive antimicrobial treatment will prolong life expectancy and decrease morbidity. It has, however, over the last decade become evident that early antimicrobial treatment of the initial infection with nonmucoid strains can prevent or at least postpone transition into chronic (mucoid) infection. This treatment strategy is likely to dramatically improve the prognosis of patients with cystic fibrosis in the immediate future.

Bronchi↗

Frequency response of fiber-optic multilayer hydrophones: experimental investigation and finite element simulation.

The frequency response of a fiber-optic hydrophone that uses a dielectric multilayer system as the sensing element for ultrasound detection is investigated. A primary interferometric calibration technique is applied to determine by experiment the frequency-dependent pressure-voltage transfer function up to 45 MHz. The interaction between an incident pressure wave and the fiber end is analyzed by finite element methods. The simulation yields the response of the sensor to a short Gaussian impulse in the time domain from which the transfer function is calculated. The results of the model simulations allowed the transfer function obtained to be interpreted as the result of the superposition of longitudinal, edge diffraction and lateral waves with a resonant vibration mode of the fiber body representing an elastic rod.

Journal Article↗