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M Kraft

Publications and source records attributed to M Kraft.

At least 37 records · Page 2Linked to original sources
PubMed2001

Decreased steroid responsiveness at night in nocturnal asthma. Is the macrophage responsible?

As peripheral blood mononuclear cells from patients with nocturnal asthma (NA) exhibit reduced steroid responsiveness at 4:00 A.M. as compared with 4:00 P.M., we hypothesized that NA is associated with increased nocturnal airway cell expression of GRbeta, an endogenous inhibitor of steroid action. Ten subjects with NA and seven subjects with nonnocturnal asthma (NNA) underwent bronchoscopy with bronchoalveolar lavage (BAL) at 4:00 P.M. and 4:00 A.M. BAL lymphocytes and macrophages were incubated with dexamethasone (DEX) at 10(-5) to 10(-8) M. DEX suppressed proliferation of BAL lymphocytes similarly at 4:00 P.M. and 4:00 A.M. in both groups. However, BAL macrophages from NA exhibited less suppression of IL-8 and TNF-alpha production by DEX at 4:00 A.M. as compared with 4:00 P.M. (p = 0.0001), whereas in the NNA group DEX suppressed IL-8 and TNF-alpha production equally at both time points. GRbeta expression was increased at night only in NA, primarily due to significantly increased expression by BAL macrophages (p = 0.008). IL-13 mRNA expression was increased at night, but only in the NA group and addition of neutralizing antibodies to IL-13 reduced GRbeta expression by BAL macrophages. We conclude that the airway macrophage may be the airway inflammatory cell driving the reduction in steroid responsiveness at night in NA, and this function is modulated by IL-13.

Adult↗
PubMed2001

Safety and reproducibility of sputum induction in asthmatic subjects in a multicenter study.

The safety of sputum induction and the reproducibility of measurements in induced sputum in multicenter studies is unknown. We examined the safety of sputum induction in a two-visit, six-center study in 79 subjects with moderate to severe asthma (mean +/- SD FEV(1) 71 +/- 12% predicted, 67% taking inhaled corticosteroids). In addition, we compared the reproducibility of markers of inflammation in induced sputum with the reproducibility of the FEV(1) and the methacholine PC(20). The FEV(1) decreased > or = 20% from the postbronchodilator baseline in 14% of all subjects and in 25% of subjects whose initial prebronchodilator baseline was 40 to 60% of predicted. All subjects responded promptly to additional albuterol treatment, and no subject developed refractory bronchoconstriction requiring treatment other than reversal of bronchospasm in the study laboratory. The reproducibility of measurements of the eosinophil percentage, eosinophil cationic protein, tryptase, and methacholine PC(20) were similar (concordance correlation coefficients of 0.74, 0.81, 0.79, and 0.74, respectively), without any significant among-center effect. We conclude that sputum induction can be performed safely in subjects with moderate to severe asthma in multicenter clinical trials when carried out under carefully monitored conditions. Importantly, we demonstrate that measurement of markers of inflammation in induced sputum is as reproducible as methacholine PC(20) and should prove useful in the assessment of airway inflammation in multicenter clinical trials.

Aged↗
PubMed2001

Distal lung dysfunction at night in nocturnal asthma.

We have previously shown that patients with nocturnal worsening of asthma (nocturnal asthma) exhibit increased parenchymal inflammation at night. To evaluate the functional significance of this parenchymal inflammation, 10 subjects with nocturnal asthma (NA), four subjects with non-nocturnal asthma (NNA), and four normal control subjects underwent bronchoscopy with measurement of peripheral airways resistance (Rp) at 4:00 P.M. and at 4:00 A.M. Employing a wedged bronchoscope technique, Rp was measured. Flow was stopped, and the pressure reached after 10 s of decay was termed the plateau pressure. The time constant of this decay (tau) was measured, and the peripheral compliance (Cp) was calculated as tau/Rp. The NA group exhibited the highest Rp values at 4:00 P.M. and at 4:00 A.M. as compared with the NNA and control groups, but all groups were significantly different from each other at 4:00 P.M.: NA, 0.113 +/- 0.02 cm H(2)O/ml/min; NNA, 0.033 +/- 0.005 cm H(2)O/ml/min; Control subjects, 0.010 +/- 0.001 cm H(2)O/ ml/min; p = 0.0001; and at 4:00 A.M.: NA, 0.129 +/- 0.023 cm H(2)O/ ml/min; NNA, 0.035 +/- 0.007 cm H(2)O/ml/min; Control subjects, 0.009 +/- 0.002 cm H(2)O/ml/min; p = 0.0003. None of the groups exhibited statistically significant differences in Rp between 4:00 P.M. and 4:00 A.M. The plateau pressure increased significantly from 4:00 P.M. to 4:00 A.M., but only in the NA group (7.7 +/- 0.9 cm H(2)O at 4:00 P.M. versus 16.9 +/- 4.6 cm H(2)O at 4:00 A.M.; p = 0.0004). Cp was decreased in the NA group as compared with the NNA and control groups at both 4:00 P.M. (p = 0.0003) and 4:00 A.M. (p = 0.003). The Rp positively correlated with the residual volume at both 4:00 P.M. (r = 0.71, p = 0.004) and 4:00 A.M. (r = 0.59, p = 0.03). We conclude that the distal lung units, specifically the collateral channels, and may be functionally altered at night in NA.

Adult↗
PubMed2001

Evaluation of persistent torticollis following adenoidectomy.

Post-operative neck complaints are not an uncommon finding following adenotonsillectomy. However, non-traumatic subluxation of the atlantoaxial joint (Grisel's syndrome) should be considered in cases of persistent neck pain and stiffness. An early diagnosis and adequate treatment of this rare condition is mandatory to prevent potentially serious complications. We describe three cases with persistent torticollis in the post-operative period, discuss the pathogenesis and evaluate the clinical management of these patients.

Adenoidectomy↗
PubMed2001

Significance of human papillomavirus in sinonasal papillomas.

Recent investigations have suggested human papillomavirus (HPV) to be involved in the development of sinonasal papillomas (SNP). Forty-three patients operated for SNP were studied to determine the prevalence of HPV-DNA sequences in these tumours and to evaluate their value as a prognostic parameter. The original sections of all cases were reviewed and reclassified according to the WHO. Paraffin blocks available from 37 patients were subjected to in situ hybridization (ISH) and polymerase chain reaction (PCR). Histology revealed 34 cases of inverted papilloma (IP) (79 per cent), five cases of exophytic papilloma (EP) (12 per cent) and four cases of columnar cell papilloma (CCP) (nine per cent). Recurrences developed in seven of 41 patients (17 per cent), and malignancy occurred in four of 43 patients (nine per cent). HPV was detected in four of 37 specimens (11 per cent) both by ISH and PCR. In particular, HPV-11 was found in three lesions (two EP, one IP) (eight per cent), and HPV-6b was detected in one lesion (one EP) (three per cent). Our findings suggest a possible role for HPV in the pathogenesis of exophytic papillomas. As no correlation was found to malignancy and recurrence of disease, screening for HPV seems not to be useful as a prognostic parameter.

Humans↗
PubMed2001

Evaluation of blood vessels and edema in the airways of asthma patients: regulation with clarithromycin treatment.

BACKGROUND: Although airway angiogenesis and edema have been proposed to contribute to the airway remodeling process in patients with asthma, there are few studies looking at these structural components in the airway tissue of asthma patients. Mycoplasma infection may be associated with chronic asthma and has been shown to induce angiogenesis and edema in a murine model. PARTICIPANTS AND MEASUREMENTS: We evaluated blood vessels and edema by immunohistochemistry in endobronchial biopsy samples from 10 normal control subjects and 15 patients with mild-to-moderate asthma before and after a 6-week treatment with clarithromycin (n = 8) or placebo (n = 7). Type IV collagen and alpha(2)-macroglobulin were used to identify blood vessels and edema in the tissue, respectively. Mycoplasma pneumoniae was evaluated by polymerase chain reaction. SETTING: National Jewish Medical and Research Center. RESULTS: At baseline, the vascularity, the number of blood vessels, and the edematous area in the airway tissue were not significantly different between asthmatic patients and normal control subjects. However, asthmatic patients demonstrated increased blood vessel size compared with normal control subjects (p = 0.03). After clarithromycin treatment in asthmatic patients, the number of blood vessels was increased (p = 0.02), while edema decreased (p = 0.049). Asthmatic patients who tested positive for M pneumoniae showed a significant increase in vascularity than asthmatic patients who tested negative for M pneumoniae (p = 0.02). CONCLUSION: Our data suggest that angiogenesis and edema may not be significant features of airway remodeling in patients with chronic, mild-to-moderate asthma. Clarithromycin treatment in asthmatic patients could reduce the edematous area as identified by alpha(2)-macroglobulin staining, which may lead to airway tissue shrinkage and cause an artificial increase in the number of blood vessels.

Adult↗
PubMed2001

Alkaline phosphatase activity: new assay for the Reflotron system. Results of the evaluation in eight clinical laboratories.

A new reagent carrier, Reflotron ALP, has been developed for the Reflotron system, allowing easy and rapid measurement (in less than 3 minutes) of alkaline phosphatase (ALP) activity in capillary blood, venous blood, heparinized plasma or serum. The evaluation of the analytical performance of the assay was carried out at eight clinical laboratories. The study of the imprecision using the measurements in human samples resulted in coefficients of variation ranging from 1.3% to 4.6% (within-run) and from 3.2% to 4.0% (day-to-day). The analytical specificity of the Reflotron ALP assay agrees well with ALP methods using a N-methyl-D-glucamine buffer solution. The calibration of the Reflotron ALP assay, however, is related to the reference intervals for ALP methods using a diethanolamine buffer solution. Method comparisons were performed with the ALP method on Hitachi instruments using diethanolamine buffer. Reflotron ALP measurements in blood and plasma in 157 randomly selected split samples showed excellent agreement (slope: 0.99; intercept: 0.7 U/l; median bias: 2.3%; median difference from the comparison method: -0.3%). Specimens from pregnant women and adolescents were excluded from this study. Differing values were obtained in a method comparison using 48 samples containing predominantly the ALP bone isoform (slope: 0.81; intercept: 31.5 U/l; median bias: 5.7%; median difference from the comparison method: -12.2%). Regression analysis of the results from 21 sera with prevailing placental ALP gave a slope of 1.51, and an intercept of -41.1 U/l (median bias: 8.6%; median difference from the comparison method: 35.6%). Reflotron ALP was compared with three different wet chemistry procedures using different buffer compounds: N-methyl-D-glucamine or diethanolamine or 2-amino-2-methyl-1-propanol. In samples containing predominantly ALP isoforms not of liver origin, the measurements with N-methyl-D-glucamine buffer gave the best fit with respect to Reflotron. In an interference study with 18 drugs, no effect on the test results could be detected. Total bilirubin up to 750 micromol/l and hemolysis up to 1.7 g/l free hemoglobin did not influence the test. Reflotron ALP proved to be an easy and rapid method with excellent precision. The accuracy related to an ALP method using diethanolamine buffer was good. The systematic differences for ALP in samples from pregnant women and adolescents have to be taken into account. The assay is well suited for differential diagnosis of hepatic diseases in decentralized testing.

Alkaline Phosphatase↗
PubMed2000

The role of bacterial infections in asthma.

In summary, bacterial organisms are clinically relevant contributors to asthma exacerbations, and have received much less attention than viruses in this process. Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis have been linked to asthma exacerbations, particularly when sinusitis is present. Treatment therefore should be directed toward these organisms if a bacterial cause is suspected. The atypical bacteria--specifically, C. pneumoniae and M. pneumoniae--deserve special attention. Data suggest a link between these organisms and the exacerbation of asthma, as well as suggest that these organisms may be causative in asthma development. The existing data are not conclusive, but are suggestive enough to drive studies evaluating them as a possible mechanism in asthma pathogenesis. An animal model evaluating M. pneumoniae and C. pneumoniae would be ideal, but at present no model exists in which chronic infection with these organisms results in bronchial hyperresponsiveness. There is active work in this area, however. Alternative investigations include continued evaluation of these organisms by several modalities, including culture, serology, and PCR, along with evaluation of the host response. Many questions remain, but the ground is fertile for continued investigation.

Asthma↗
PubMed2000

Substance P and its receptor neurokinin 1 expression in asthmatic airways.

BACKGROUND: Neural mechanisms have been suggested to contribute to the pathogenesis of chronic asthma. The expression of neuropeptides such as substance P may be regulated by infectious pathogens, including Mycoplasma species. In contrast to substance P, the substance P receptor neurokinin 1 has not been examined at the protein level in asthmatic airways. OBJECTIVE: This study evaluated substance P and neurokinin 1 protein expression and mucus content in endobronchial biopsy specimens from normal control subjects and asthmatic subjects. Detection of Mycoplasma pneumoniae was performed in both biopsy and bronchoalveolar lavage specimens. METHODS: Biopsy specimens were collected from 10 normal control subjects and 18 asthmatic subjects before and after a 6-week treatment with a macrolide antibiotic (n = 11) or placebo (n = 7) and were stained for substance P, neurokinin 1, and mucus. M pneumoniae was evaluated by PCR. RESULTS: At baseline, compared with normal control subjects, asthmatic subjects demonstrated increased expression of substance P and neurokinin 1 and mucus content in the airway epithelium. Epithelial mucus content correlated with epithelial substance P expression (r (s) = 0.45, P =.04) and FEV(1) percent predicted (r (s) = -0.51, P =.019). After antibiotic treatment, both epithelial substance P and neurokinin 1 expression were significantly reduced in asthmatic subjects. M pneumoniae was found in 8 of 18 asthmatic subjects. Asthmatic subjects with M pneumoniae, compared with those without M pneumoniae, showed higher baseline epithelial neurokinin 1 expression, which was significantly reduced after antibiotic treatment (P =.02). CONCLUSION: Our data suggest that abnormalities in neural mechanisms may exist in the epithelium of asthmatic airways, and M pneumoniae is possibly involved in this process. Antibiotic intervention may be effective in the treatment of asthma partly through the downregulation of the neurogenic process.

Adult↗
PubMed2000

The effect of polymorphisms of the beta(2)-adrenergic receptor on the response to regular use of albuterol in asthma.

Inhaled beta-adrenergic agonists are the most commonly used medications for the treatment of asthma although there is evidence that regular use may produce adverse effects in some patients. Polymorphisms of the beta(2)-adrenergic receptor (beta(2)-AR) can affect regulation of the receptor. Smaller studies examining the effects of such polymorphisms on the response to beta-agonist therapy have produced inconsistent results. We examined whether polymorphisms at codon 16 (beta(2)-AR-16) and codon 27 (beta(2)-AR-27) of the beta(2)-AR might affect the response to regular versus as-needed use of albuterol by genotyping the 190 asthmatics who had participated in a trial examining the effects of regular versus as needed albuterol use. During the 16-wk treatment period there was a small decline in morning peak expiratory flow in patients homozygous for arginine at B(2)-AR-16 (Arg/Arg) who used albuterol regularly. This effect was magnified during a 4-wk run out period, during which all patients returned to using as-needed albuterol, so that by the end of the study Arg Arg patients who had regularly used albuterol had a morning peak expiratory flow 30. 5 +/- 12.1 L/min lower (p = 0.012) than Arg/Arg patients who had used albuterol on an as needed basis. There was no decline in peak flow with regular use of albuterol in patients who were homozygous for glycine at beta(2)-AR-16. Evening peak expiratory flow also declined in the Arg/Arg patients who used albuterol regularly but not in those who used albuterol on an as-needed basis. No significant differences in outcomes between regular and as-needed treatment were associated with polymorphisms at position 27 of the beta(2)-AR. No other differences in asthma outcomes that we investigated occurred in relation to these beta(2)-AR polymorphisms. Polymorphisms of the beta(2)-AR may influence airway responses to regular inhaled beta-agonist treatment.

Adolescent↗
PubMed2000

Frontline immunochromatographic device for on-site urine testing of amphetamines: laboratory validation using authentic specimens.

We evaluated a new test device for amphetamines and methamphetamines (Frontline, cut-off limit 300 ng/mL) using authentic clinical and forensic specimens. The device is based on immunochromatography and is dipped into urine and read visually by comparison with a colour scale after a few minutes. A total of 658 specimens were tested by comparing results of the screening procedure with established immunoassays. Discordant results were further investigated by gas chromatography mass spectrometry or gas chromatography (with flame ionization detector). The Frontline device had a sensitivity of 93% and a specificity of 98%. When specimens were classified by urine amphetamine concentration, close agreement was obtained at concentrations below 150 ng/mL and above 1000 ng/mL. A small number of specimens with amphetamine concentrations between 300 and 1000 ng/mL tested negative in the Frontline test. This finding could to some extent be explained by the enantioselectivity of the antibodies in the Frontline test to d-amphetamine. We conclude that the performance of the Frontline test device for amphetamines is adequate for presumptive clinical and forensic screening.

Amphetamines↗
PubMed2000

Serum lidocaine concentrations in asthmatics undergoing research bronchoscopy.

STUDY OBJECTIVES: To determine how often serum lidocaine concentrations (SLC) fall into the potentially toxic range (> 5 mg/L) in asthmatics undergoing research bronchoscopy, and to determine whether subject or procedure characteristics are associated with higher SLC. DESIGN: Prospective, observational study. SETTING: Academic research center. PARTICIPANTS: Fifty-one volunteers with mild to moderate asthma enrolled in three separate bronchoscopy protocols to study airway inflammation in asthma. INTERVENTIONS: Lidocaine was administered topically to the upper airway and tracheobronchial tree to achieve local anesthesia for bronchoscopy. Venous blood was sampled during bronchoscopy, 30 min after upper airway anesthesia was completed (time 1), and 30 min after bronchoscopy was completed (time 2). MEASUREMENTS AND RESULTS: The mean total amount of lidocaine administered was 600 +/- 122 mg (8.2 +/- 2.0 mg/kg). No signs or symptoms of lidocaine toxicity were observed in any of the subjects. SLC ranged between 0.10 and 2.90 mg/L at time 1 and 0.50 and 3.20 mg/L at time 2. SLC was significantly correlated with the total amount of lidocaine (milligrams/kilogram) administered at both points (time 1, r = 0.33, p = 0.021; time 2, r = 0.33, p = 0.023). No statistically significant relationship was observed between SLC and subject age, sex, weight, baseline FEV(1), procedure length, or study protocol. No statistically significant relationship was found between subject FEV(1) and either total lidocaine dose or procedure length. CONCLUSIONS: An average total dose of 600 mg (8.2 mg/kg) of lidocaine appears to be safe in mild to moderate asthmatics undergoing research bronchoscopy.

Academic Medical Centers↗
PubMed2000

[Multifunctional testing of PTCA balloon catheters].

New in vitro measuring methods for balloon catheters used for percutaneous transluminal coronary angioplasty (PTCA) and their verification in a complex test device are presented. This system can mimic all relevant application situations. The central element of the test device is a coronary vessel model matching the physiological situation in terms of geometrical structure and frictional properties. Reactive force sensors are used to measure the application-relevant forces exerted by the catheter on the model vessel walls and accessories, such as guide wire and guiding catheter. To generate a kink-free advancement of the catheter and permit measurement of the active forces, an alternating drive unit has been specially developed. The testing and application of the newly developed methods revealed statistically significant differences between various types of catheter. The test device closes a gap between complex but subjective clinical tests, and individual objective, but application-removed in vitro test setups for PTCA catheters. While the initial prototype had shortcomings with regard to the reproducibility of measurements, successor systems developed for industrial use are now in production. The properties of these measuring systems developed for the benefit of manufacturer and reprocessor of PTCA catheters are discussed.

Angioplasty, Balloon, Coronary↗
PubMed2000

[Reuse of instruments for minimal invasive surgery--status and prospects].

The development of instruments for minimal invasive surgery (MIS) is moving in the direction of the miniaturization of mechanical components, a combination of multiple functions in a single instrument, and the introduction of new techniques, in particular those reducing bleeding and thermal damage when cutting blood vessels. These tendencies have consequences for the reprocessability of the instruments, usually making reprocessing more difficult. In particular cleaning--the removal of contaminations from tiny lumina, joints, etc., is highly demanding. In addition, proof of successful cleaning is difficult, and no standardised method of doing this in practice is currently available. An overview of the problems associated with the reprocessing of instruments for minimal invasive surgery is given, and a numbers of possible solutions are discussed.

Endoscopes↗
PubMed2000

[Significance of human papillomaviruses (HPV) in sinonasal papillomas].

The present study comprises 43 patients with sinonasal papillomas operated on between 1990 and 1997 at the ENT Department, University Hospital of Zurich. Histology showed 5 cases of exophytic papilloma (EP) (12%), 34 cases of inverted papilloma (IP) (79%) including 4 cases of associated carcinoma (9%), and 4 cases of columnar cell papilloma (CCP) (9%). Recurrence developed in 6 of 41 patients (2 EP, 4 IP) (15%). HPV was detected in 4 of 37 specimens (11%) both by in situ hybridization (ISH) and polymerase chain reaction (PCR). HPV-11 was found in 3 lesions (2 EP, 1 IP), whereas HPV-6b was detected only in one lesion (1 EP). Altogether 3 of 5 EP (60%), one of 29 IP (3%) and one of 6 recurrent papillomas (1 EP) (17%) tested positive for HPV. Our findings suggest a possible role for HPV in the pathogenesis of exophytic papilloma. As no correlation was found with associated malignancy and recurrence of disease, screening for HPV seems not to be useful as a prognostic parameter.

Cell Transformation, Neoplastic↗
PubMed1999

Induction of Fas ligand expression by HIV involves the interaction of Nef with the T cell receptor zeta chain.

During HIV/SIV infection, there is widespread programmed cell death in infected and, perhaps more importantly, uninfected cells. Much of this apoptosis is mediated by Fas-Fas ligand (FasL) interactions. Previously we demonstrated in macaques that induction of FasL expression and apoptotic cell death of both CD4(+) and CD8(+) T cells by SIV is dependent on a functional nef gene. However, the molecular mechanism whereby HIV-1 induces the expression of FasL remained poorly understood. Here we report a direct association of HIV-1 Nef with the zeta chain of the T cell receptor (TCR) complex and the requirement of both proteins for HIV-mediated upregulation of FasL. Expression of FasL through Nef depended upon the integrity of the immunoreceptor tyrosine-based activation motifs (ITAMs) of the TCR zeta chain. Conformation for the importance of zeta for Nef-mediated signaling in T cells came from an independent finding. A single ITAM motif of zeta but not CD3epsilon was both required and sufficient to promote activation and binding of the Nef-associated kinase (NAK/p62). Our data imply that Nef can form a signaling complex with the TCR, which bypasses the requirement of antigen to initiate T cell activation and subsequently upregulation of FasL expression. Thus, our study may provide critical insights into the molecular mechanism whereby the HIV-1 accessory protein Nef contributes to the pathogenesis of HIV.

Fas Ligand Protein↗
PubMed1999

Nocturnal asthma is associated with reduced glucocorticoid receptor binding affinity and decreased steroid responsiveness at night.

BACKGROUND: The mechanisms for heightened nocturnal inflammation in patients with nocturnal asthma (NA) are not well understood. OBJECTIVE: We sought to determine the glucocorticoid receptor (GR) characteristics and steroid responsiveness in subjects with NA. METHODS: Eleven subjects with NA, 12 subjects with nonnocturnal asthma (NNA), and 16 nonasthmatic control subjects underwent blood sampling at 4 pm and 4 am in a random order separated by 1 week. GR binding affinity was measured in PBMCs by using a [3H]-dexamethasone (DX) radioligand binding assay and Scatchard analysis. The capacity of hydrocortisone (HC) and DX to suppress proliferation of PBMCs stimulated with PHA was also determined. RESULTS: The subjects with NA exhibited a significantly lower GR binding affinity at 4 am, detected by an elevated dissociation constant (Kd) of 22.2 +/- 1.6 nmol/L compared with Kd at 4 pm (10.9 +/- 0.7 nmol/L; P =.0001). The GR Kd of the NNA and control groups did not change significantly from 4 pm to 4 am. Within the NA group, there was also a significant inverse correlation between the absolute FEV1 at 4 am and the Kd at 4 am (r = -0.65, P =.04). PBMCs from subjects with NA exhibited less suppression of PBMC proliferation with HC and DX at 4 am compared with that at 4 pm (P =.0004 and.03 for HC and DX, respectively). There were no circadian changes in suppression of PBMC proliferation in either the NNA or control groups. CONCLUSION: GR binding affinity and steroid responsiveness exhibit a circadian variation in subjects with NA, with a reduced GR binding affinity and suppression of PBMC proliferation at 4 am that is not observed in normal subjects or asthmatic subjects without nocturnal exacerbation. These observations may contribute to nocturnal airway inflammation by inhibiting the antiinflammatory effects of glucocorticoids.

Adult↗