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Biomedical subjects

H G Wiesemann

Publications and source records attributed to H G Wiesemann.

At least 19 recordsLinked to original sources

Airway nitric oxide in infants with acute wheezy bronchitis.

Concentrations of nitric oxide (NO) in exhaled air are increased in children and adults with asthma, and NO measurements are used as a non-invasive marker to monitor airway inflammation in these patients. To define the role of NO in infants with acute wheezy bronchitis, we measured nasal and end-tidal NO concentrations in 17 infants with acute virus-associated wheezy bronchitis, in 22 term infants without respiratory disease, and in nine premature infants. Nasal NO measurements were performed with an olive placed in the infant's nose; end-tidal NO concentrations were assessed during tidal breathing through a snuggly fitting face mask. Both end-tidal NO concentrations and nasal NO concentrations were reduced in infants with acute wheezy bronchitis. There were no differences in NO concentrations between term infants and premature infants. Measurements by both techniques were highly reproducible, as assessed by repeated measurements three times daily on three consecutive days in eight premature infants. Reduced airway NO concentrations in infants with virus-associated acute wheezy bronchitis are in contrast to findings in adults where both upper and lower airway NO levels are increased in patients with asthma. Whether this reflects a different inflammatory reaction to upper airway infections in acutely wheezy infants or pathophysiologic differences in airway response remains to be determined.

Acute Disease↗

Effect of inhaled nitric oxide on pulmonary function in cystic fibrosis.

Concentrations of nitric oxide (NO) have been found to be reduced in both the upper and lower airway of patients with cystic fibrosis (CF). As NO modulates bronchomuscular tone, low NO levels may contribute to the obstructive lung disease in these patients. To assess whether increasing inspiratory NO concentrations has any impact on lung function, we have studied 13 CF patients aged 14-38 years in a clinically stable condition and nine healthy controls. NO was applied via a mixing chamber for 5 min with NO concentrations of 100 parts per billion, 1 and 40 parts per million. Spirometry was performed at baseline and after inhalation on each occasion. There were no clinical side-effects at any NO concentration and no changes in oxygen saturation were observed. Lung function remained unchanged in all subjects throughout the study period. Sputum nitrate and nitrite concentrations before and after inhalation of high NO concentrations (40 ppm) in eight CF patients did not show any significant changes, even though a tendency to higher nitrate levels was observed (399 +/- 231 vs. 556 +/- 474 mumol l-1). Therefore, inhaled NO at either the physiological levels present in the upper airway of normal individuals or those used therapeutically to treat pulmonary hypertension has no immediate effect on bronchomuscular tone in patients with cystic fibrosis.

Administration, Inhalation↗

Effect of L-arginine infusion on airway NO in cystic fibrosis and primary ciliary dyskinesia syndrome.

Airway nitric oxide concentrations in patients with cystic fibrosis or primary ciliary dyskinesia syndrome have been shown to be lower than in healthy subjects. Decreased NO concentrations may contribute to impaired ciliary clearance, respiratory tract infections, or obstructive lung disease in these conditions. Nasal and exhaled NO concentrations were compared before and after infusion of 500 mg x kg(-1) L-arginine, the substrate of NO synthases, in 11 cystic fibrosis (CF) patients, seven primary ciliary dyskinesia (PCD) syndrome patients, and 11 control subjects. Baseline nasal and exhaled NO concentrations were significantly lower in both CF and PCD syndrome patients than in controls (p<0.01). In controls, the maximum increase of NO was seen immediately after L-arginine infusion in the upper airways (1.8-fold) and 3 h after the infusion in the lower airways (1.4-fold). Although NO concentrations also increased significantly in both CF (1.9-fold and 1.6-fold, respectively) and PCD syndrome patients (1.4-fold and 1.8-fold, respectively), concentrations remained subnormal compared with baseline values of controls. Pulmonary function remained unchanged in both patient groups. In conclusion, the low airway nitric oxide formation in both cystic fibrosis and primary ciliary dyskinesia syndrome patients can be augmented by L-arginine administration. The finding that pulmonary function remained unchanged in both conditions may be due to the fact that normalization of airway nitric oxide concentrations could not be achieved.

Adolescent↗

Placebo-controlled, double-blind, randomized study of aerosolized tobramycin for early treatment of Pseudomonas aeruginosa colonization in cystic fibrosis.

In chronic Pseudomonas aeruginosa pulmonary infection of patients with cystic fibrosis (CF), antibiotic therapy generally fails to eradicate the bacterial pathogen. The mucoid bacterial phenotype, high sputum production by the host, and low airway levels of antibiotics seem to be responsible for the observed decrease in antibiotic efficacy. We hypothesized that early antibiotic treatment by inhalation in CF patients may be able to prevent or at least delay airway infection. In a prospective placebo-controlled, double-blind, randomized multicenter study, 22 CF patients received either 80 mg b.i.d. of aerosolized tobramycin or placebo for a period of 12 months shortly after the onset of P. aeruginosa pulmonary colonization. Two patients in the tobramycin and six patients in the placebo group stopped inhalation before the 12 month treatment period. Using life table analysis, the time to conversion from a P. aeruginosa-positive to a P. aeruginosa-negative respiratory culture was significantly shorter in the tobramycin-treated group than in the placebo group (P < 0.05, log rank test). Lung function parameters and markers of inflammation did not change in either group during treatment. The results of this study suggest that early tobramycin inhalation may prevent and/or delay P. aeruginosa pulmonary infection in CF patients.

Administration, Inhalation↗

Isovolume pressure/flow curves of rapid thoracoabdominal compressions in infants without respiratory disease.

To assess whether flow limitation can be achieved during rapid thoracoabdominal compressions (RTC), we performed esophageal pressure measurements in 11 healthy infants less than 3 months of age. Recordings of esophageal pressure were obtained with an esophageal balloon placed in the lower esophagus. RTCs were started at 20 cm H2O and increased to 140 cm H2O or until the infant responded with glottic closure to the compression. Flow limitation was assessed from isovolume pressure flow curves at peak flow and flow at FRC (V'max, FRC). The transmission of jacket pressure was higher at peak flow than at FRC for pressures below 60 cm H2O, due to active inspiration during the compression. Active inspiration was not observed at compression pressures above 80 cm H2O, as reflected by a plateau in the esophageal pressure tracing. Esophageal pressure increased parallel to the compression pressure at jacket pressures below 60 cm H2O. The relationship between jacket pressure and esophageal pressure became curvilinear at high compression pressures and plateaued at compressions above 100 cm H2O, so that further increases in jacket pressure did not increase esophageal pressure. Flow limitation was seen in all infants studied, as indicated by a lack of increase in flow with increasing esophageal pressures for V'max, FRC. Jacket compression pressures of 60 cm H2O and esophageal pressures of 20 cm H2O were sufficient to reach maximal expiratory flow. These data indicate that jacket pressure is a poor indicator of pleural pressure at high compression pressures in young healthy infants, and high pressures are not needed, as flow limitation is seen during RTCs at moderate compression pressures.

Esophagus↗

The effect of rapid thoracoabdominal compressions on intracranial pressure in newborn lambs.

Measurements of forced expiratory flow in infants can be obtained with the rapid thoracoabdominal compression (RTC) technique. To assess the transmission of the chest wall compression pressure into the cerebrum, we have performed intracranial pressure (ICP) measurements during RTCs in newborn lambs. Thirteen lambs were studied during the first 8 d of life. An epidural pressure transducer was implanted under general anesthesia. Respiratory measurements were performed under sedation with ketamine. RTCs were induced through an inflatable jacket wrapped around the lamb's trunk. RTCs were started with a pressure of 30 cm H2O. The compression pressure was increased in steps of 20 cm H2O up to 250 cm H2O. Flow and volume were determined with a pneumotachograph attached to a face mask. Transpulmonary pressure (Ptp) was measured with an esophageal balloon placed in the lower esophagus. RTCs resulted in proportional increases of Ptp and ICP. ICP was lower or equal to Ptp in all measurements. No changes in baseline ICP occurred throughout the study period. The maximal ICP observed during RTCs was within the range of pressures observed during crying in newborn infants. These data suggest that the RTC technique can be considered safe even at high compression pressures.

Animals↗

[The importance of lung function as a predictor of 2-year mortality in mucoviscidosis].

Prediction of mortality in cystic fibrosis (CF) has become an important issue in the era of lung transplantation. A study from Toronto has shown a forced expiratory volume in one second (FEV1) below 30% predicted to be the best predictor of two-year mortality. The purpose of this investigation was to assess whether these data are relevant for other CF centers with a different overall life expectancy. We have analysed pulmonary function tests (PFTs) obtained in our population of CF patients between 1979 and 1991. 19 of the 73 patients included in this analysis had died. Cox proportional hazard regression analysis was performed using the lung function parameters as single covariates. In addition results of PFTs obtained two years before death were compared to similarly lagged values of surviving patients. Inspiratory vital capacity (IVC) (p < 0.0001), the ratio of residual volume/total lung capacity (RV/TLC) (p < 0.0001), forced expiratory volume in one second (FEV1) (p < 0.0002), specific conductance (sGaw) (p < 0.025) and a weight for height below the third percentile (p < 0.023) were significant predictors of two-year mortality. Two-year mortality were 50% for a FEV1 < 30% predicted and 47% for a RV/TLC ratio > 50%. Our data confirm that a FEV1 < 30% and a RV/TLC ratio > 50% are significant predictors of mortality in CF. However, interindividual variability in survival with a FEV1 < 30% is high. The decision for lung transplantation can therefore not be based on pulmonary function alone.

Adolescent↗

Variability of dynamic compliance measurements in spontaneously breathing and ventilated newborn infants.

We studied reproducibility and variability of dynamic pulmonary compliance (Cdyn) by making measurements with the esophageal balloon at multiple locations within the esophagus, in both spontaneously breathing and mechanically ventilated newborn infants. Reliable measurements could be obtained over a range similar to that reported for measurements with a liquid-filled catheter. In spontaneously breathing infants Cdyn was found to be highly variable. This variability was unrelated to catheter position but was associated with concomitant changes in pulmonary resistance. Probably because of the high variability, the correlation of Cdyn with a measurement of respiratory system compliance (Crs) was rather poor (r = 0.63). Cdyn measured in mechanically ventilated infants was significantly less variable and compared favorably to Crs (r = 0.86), but its accuracy could not be adequately assessed since the comparison of esophageal and airway occlusion pressure was not feasible in all infants. In addition, significant differences in Cdyn were found between spontaneous and ventilated breaths during mechanical ventilation. Further studies in both ventilated and spontaneously breathing infants are needed to assess the variability of Cdyn over extended time periods.

Catheterization↗

Pulmonary alveolar microlithiasis and lymphocytic interstitial pneumonitis in a ten year old girl.

Pulmonary alveolar microlithiasis (PAM) is a rare lung disease, characterized by progressive formation of intra-alveolar calculi in response to an unknown stimulus. We report an unusual presentation of PAM in a 10 year old girl with clinically significant interstitial lung disease and histological evidence of both PAM and lymphocytic interstitial pneumonitis. A rapid improvement of pulmonary function and exercise tolerance was seen in response to glucosteroid therapy.

Bronchoalveolar Lavage Fluid↗

Clinical efficacy of two beta 2-sympathicomimetics in different inhalers in children with asthma. Comparison of pirbuterol in a breath-actuated inhaler and salbutamol in a customary metered-dose inhaler.

In a controlled clinical crossover trial, the therapeutic effect of pirbuterol (CAS 38677-81-5) in the Autohaler was compared to that of salbutamol in a customary metered-dose aerosol in 17 children with asthma. Each child was randomized to both treatments with a washout period of at least 1 day and at most 13 days. Ten children commenced with salbutamol and then switched over to pirbuterol, and the other 7 vice versa. The main criterion to evaluate efficacy was the forced expiratory volume after 1 s (FEV1). Other efficacy criteria were forced vital capacity (FVC) and peak expiratory flow (PEF). The patients were given detailed instructions on how to use the inhalers. Each treatment was applied in the morning with one shot (0.2 mg pirbuterol or 0.1 mg salbutamol). FEV1, FVC and PEF were measured in all patients 10 min before and 10 min after medication with the whole-body plethysmograph; further measurements were carried out in most patients 60 and 240 min after application. There was a mean increase of 47% in the FEV1 compared to baseline with pirbuterol in the Autohaler compared to a mean increase of only 30% with salbutamol in the customary metered-dose inhaler. The difference is statistically significant (p = 0.036). A linear crossover analysis showed a significant treatment effect 10 min after application in favour of pirbuterol with no significant period effects or interactions (p = 0.020). The increases of FVC and PEF after pirbuterol treatment were also remarkably higher than after salbutamol. No side effects were observed.

Administration, Inhalation↗

[Antibiotic pharmacokinetics in patients with mucoviscidosis].

In this review we summarize the available literature on the pharmacokinetics of antibacterials in cystic fibrosis. A special impact is given on the results of our group which will be put in perspective with the results of other authors. The homogeneity of our patient population allows a valid comparison between patient and volunteer data. We do not confirm the previously suggested strongly enhanced elimination of antibacterials in CF. Our findings have recently been confirmed by other investigators. However, since in the clinical situation a more heterogeneous group of patients is treated it seems rational to increase the dose of the antibacterials by about 20-30%.

Anti-Bacterial Agents↗

[Comparison of 2 pancreatic enzyme preparations in the treatment of digestive insufficiency in mucoviscidosis (cystic fibrosis)].

In an open trial 10 patients with cystic fibrosis were treated with two acid-protected pancreatic enzyme preparations formed as microtablets or pellets. The difference between Panzytrat 20,000 and Kreon is that with only 225 mg pancreatin, the former has twice the lipase activity of the latter. Therefore, the patients who had been taken Kreon were given only half the number of Panzytrat 20,000 capsules. There were no significant differences seen between the amounts of fecal fat nor in the fecal weight. In our study the fat absorption coefficient was somewhat too low with 67.4% for Kreon and 71.3% for Panzytrat 20,000 because of too low enzyme dosage, which was based only on an improvement of the clinical symptoms. Therefore, we would recommend a higher dose of 1000-1500 units of lipase/l g of dietary fat ingested. This requires the use of a preparation with high enzyme activity.

Adolescent↗

[Spontaneous pneumothorax in cystic fibrosis].

The clinical course of 13 cystic fibrosis patients with a total of 24 episodes of pneumothorax was analysed. The study is based on 488 (273/215) patients seen over 20 respectively 10 years at the University Children's Hospitals Frankfurt/Main and Essen. A pneumothorax was observed with a frequency of 2.7% mainly in adolescents of young adults with advanced pulmonary disease (mean age 17.4 years). It was not seen before the age of 10 years. Thus among 255 patients at risk above 10 years a pneumothorax occurred in 5.1%. Presenting symptoms were acute chest pain (n = 17), dyspnea (n = 17) and irritating cough (n = 8). In two patients pneumothorax was an incidental diagnosis. A tension pneumothorax was seen in 7 (= 30%; 3 initial, 4 recurrences of which 3 were ipsilateral). Out of 11 recurrences (n = 6, ipsi- and n = 5, contralateral) 4 occurred only once, one twice and in one patient five times. Two patients died as a consequence of the event (one initially due to tension pneumothorax, one due to heart failure). The therapeutic approach was conservative. Without specific treatment pneumothorax resolved in 12 cases. Ten patients were treated by chest tube drainage and only one patient by pleurodesis with a sclerosing agent. Though the therapeutic results were favorable in the patients presented, the authors suggest more aggressive treatment in view of the high ipsilateral recurrence rate. Detailed recommendations are given.

Child↗

High dose treatment with antibiotics in cystic fibrosis--a reappraisal with special reference to the pharmacokinetics of beta-lactams and new fluoroquinolones in adult CF-patients.

In this review we analyzed the pharmacokinetic basis for high dose treatment with antibiotics of patients with cystic fibrosis. Both our results and those from other well designed pharmacokinetic studies do not support the view that low blood levels of antibacterials are a common feature of CF. We were unable to detect a decrease in absorption, nor could we find evidence for enhanced elimination of antibacterials in CF. Both these factors have been considered responsible for reducing the plasma (and tissue) levels of antibiotics. Most recent studies on kidney function are in agreement with these findings, since neither inulin nor creatinine clearance differ between CF-patients and healthy volunteers. In contrast to previous discussion, the volume of distribution (Vdss) was not elevated for any compound. The rational of weight correction of volume terms like Vdss or total clearance has never been clearly demonstrated and should therefore not be used without prior proof of relevance. Since the variability of pharmacokinetic parameters of antibiotics in CF-patients may be considerable, we suggest that a dose increase of 20-30% may be justified, but cannot agree with two to fourfold increases in dosage as previously proposed and applied in many CF-centers. Until more findings become available for non-adult CF-patients, these conclusions are only valid for adult CF-patients.

Anti-Bacterial Agents↗

[Sonographic findings in the gallbladder in mucoviscidosis patients].

The improved survival time of patients with mucoviscidosis has revealed some new complications. 137 patients were studied by sonography. The findings in the gall bladder have been compared with liver echogenicity. A micro-gall bladder was found in 37 patients (27%). 74 patients had a normal gall bladder (54%). Concretions were found in 22 (16%) of patients. 10 out of the 22 patients with concretions showed sonographic changes in the liver. In view of the frequent abdominal symptoms in patients with mucoviscidosis, sonography should be used routinely as a non-invasive method of investigation.

Adolescent↗

Auditory brainstem response (ABR) in congenital central alveolar hypoventilation.

Auditory brainstem responses (ABRs) were studied in a child with congenital central alveolar hypoventilation showing marked depression of respiratory drive during sleep. During wakefulness and normoventilation no ABR abnormalities were found, either at the age of 14 months or five years. ABR recordings during sleep at 14 months of age showed marked wave V latency and wave I to wave V interpeak latency prolongation of about 0.4 ms both for periods of hypoventilation and normoxic hypercapnia. ABR findings of this and other studies carried out in sleep apneas are discussed with respect to brainstem dysfunction associated with varied sleep apnea syndromes.

Brain Stem↗

Associations of personality variables with smoking behavior and pulmonary function.

Interindividual variability of lung function responses to smoking is unexplained. The aim of the present study is to inquire about a possible role of personality factors for an explanation of interindividual differences of lung function responses in smokers of both sexes. The results of canonical correlation analyses showed that there are no substantial correlations of personality with smoking behavior and also no significant associations of smoking behavior with pulmonary function in a healthy sample of smokers. In males only, personality factors were related to breathing frequency, but not to static and dynamic lung volumes.

Adolescent↗