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  • 1
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Kongress Medizin und Gesellschaft 2007; 20070917-20070921; Augsburg; DOC07gmds344 /20070906/
    Publication Date: 2007-09-07
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 2
    Keywords: CANCER ; INVASION ; tumor ; Germany ; LUNG ; lung cancer ; LUNG-CANCER ; DISEASE ; RISK ; GENE ; SAMPLE ; TISSUE ; TISSUES ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; BREAST-CANCER ; HEALTH ; PROMOTER ; AGE ; METASTASIS ; smoking ; COLORECTAL-CANCER ; REGION ; REGIONS ; EXTRACELLULAR-MATRIX ; OVEREXPRESSION ; MMP ; MATRIX ; ONCOLOGY ; RE ; INCREASE ; MATRIX METALLOPROTEINASES ; SINGLE NUCLEOTIDE POLYMORPHISMS ; SNPs ; intensity ; TUMOR TISSUE ; biomarker ; analysis ; HAPLOTYPE ; GENOTYPE DATA ; USA ; cancer research ; CIGARETTE-SMOKE ; matrix metalloproteinase ; MATRIX-METALLOPROTEINASE ; GENE POLYMORPHISM ; NUCLEOTIDE ; MATRIX METALLOPROTEINASE-1 ; METALLOPROTEINASE-1 PROMOTER POLYMORPHISM ; TISSUE INHIBITORS
    Abstract: Matrix metalloproteinases (MMP) play a key role in the breakdown of extracellular matrix and in inflammatory processes. MMP1 is the most highly expressed interstitial collagenase degrading fibrillar collagens. Overexpression of MMP1 has been shown in tumor tissues and has been suggested to be associated with tumor invasion and metastasis. Nine haplotype tagging and additional two intronic single nucleotide polymorphisms (SNP) of MMPI were genotyped in a case control sample, consisting of 635 lung cancer cases with onset of disease below 51 years of age and 1,300 age- and sex-matched cancer-free controls. Two regions of linkage disequilibrium (LD) of MMP1 could be observed: a region of low LD comprising the 5' region including the promoter and a region of high LD starting from exon 1 to the end of the gene and including the 3' flanking region. Several SNPs were identified to be individually significantly associated with risk of early-onset lung cancer. The most significant effect was seen for rs1938901 (P = 0.0089), rs193008 (P = 0.0108), and rs996999 (P = 0.0459). For rs996999, significance vanished after correction for multiple testing. For each of these SNPs, the major allele was associated with an increase in risk with an odds ratio between 1.2 and 1.3 (95% confidence interval, 1.0-1.5). The haplotype analysis supported these findings, especially for subgroups with high smoking intensity. In summary, we identified MMPI to be associated with an increased risk for lung cancer, which was modified by smoking
    Type of Publication: Journal article published
    PubMed ID: 18483334
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  • 3
    Keywords: APOPTOSIS ; CANCER ; EXPRESSION ; GROWTH ; INHIBITOR ; CELL ; Germany ; LUNG ; MODEL ; MODELS ; lung cancer ; LUNG-CANCER ; POPULATION ; RISK ; GENE ; PROTEIN ; PATIENT ; MECHANISM ; CARCINOGENESIS ; mechanisms ; CELL-CYCLE ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; SUSCEPTIBILITY ; NO ; DIFFERENCE ; PROMOTER ; AGE ; WOMEN ; CIGARETTE-SMOKING ; smoking ; p53 ; REGION ; MDM2 ; HEALTHY ; DNA repair ; protein expression ; CELL-GROWTH ; ONCOLOGY ; RE ; SUBTYPES ; GENOTYPE ; GENDER ; PROMOTER REGION ; ENGLAND ; CIGARETTE ; interactions ; ACCELERATES TUMOR-FORMATION ; SNP309
    Abstract: The polymorphism SNP309 (rs2279744) in the promoter region of the MDM2 gene has been shown to alter protein expression and may play a role in the susceptibility to lung cancer. The MDM2 protein is a key inhibitor of p53 and several mechanisms of MDM2/p53 interactions are presently known: modulating DNA-repair, cell-cycle control, cell growth and apoptosis. We used 635 Caucasian patients diagnosed with lung cancer before 51 years of age and 1300 healthy gender and age frequency matched population Caucasian controls to investigate the association between the MDM2 SNP309 and the risk of developing early onset lung cancer. Conditional logistic models were applied to assess the genotype-phenotype association, adjusted for smoking. Compared to the GG genotype, the adjusted ORs for the TG and TT genotype were 0.9 (95% CI: 0.7-1.5) and 1.0 ( 95% CI: 0.7-1.5), respectively. Also no association was found for histological subtypes of lung cancer. The strength of this study is that within young cases the genetic component to develop lung cancer may be greater. Our results indicate that the MDM2 SNP309 is not significantly associated with lung carcinogenesis but point towards gender-specific differences
    Type of Publication: Journal article published
    PubMed ID: 18433484
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  • 4
    ISSN: 1432-1041
    Keywords: enprofylline ; theophylline ; bronchial reactivity ; histamine inhalation test ; healthy volunteers ; pharmacokinetics ; bronchodilatation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double blind, placebo controlled, crossover study the pharmacokinetics and acute effects of enprofylline and theophylline on airway reactivity during histamine challenge were investigated in 10 healthy volunteers. The pharmacokinetic parameters of enprofylline were (mean): elimination half-life 1.9 h, total body clearance 191.1 ml · kg−1 · h−1, volume of distribution 0.48 l · kg−1, and protein binding 49%. Bronchial reactivity in the histamine inhalation test was expressed as the concentration causing a 20% fall in FEV1.0 (PC20). Mean PC20 values were lowest after placebo and highest after theophylline with the enprofylline values in between. Only the difference in PC20 Safter placebo and theophylline was statistically significant (p〈0.05). At the time of determination of the PC20, the serum concentration of enprofylline was between 16.5 and 11.8 µmol/l, and that of theophylline was between 78.3 and 61.1 µmol/l. Adverse actions of enprofylline were nausea (3/10) and cardiovascular reactions (2/10), whereas theophylline mainly caused restlessness (3/10) and tremor (2/10). Thus enprofylline, in one-fifth of the serum concentration of theophylline cannot be regarded as equipotent in terms of bronchoprotection.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1041
    Keywords: theophylline ; computer simulation ; pharmacokinetics ; single-point dose prediction ; nomogram
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A dosage prediction method to estimate theophylline clearance and dose requirement was evaluated in 22 outpatients with partly reversible obstructive airways disease. The steady state theophylline dose required to achieve a target concentration (Css) was predicted using a single serum theophylline determination 8 h after a single oral test dose. In 17 nonsmoking patients a mean absolute deviation of 8.2% (range 0.0–21.7%) between predicted and observed Css was found, and in 5 smoking patients the mean deviation was 34.0% (range 2.2–53.8%). In 17 healthy smokers the single-point method was found to predict theophylline clearance at a sampling time of 8 h with a prediction error of 11.3 (range 0.8–25.3%) compared to the clearance determination using the area under the curve. In addition, a numerical simulation program to assess the influence of absorption, elimination and sampling time on predictive accuracy showed that the method could be successfully applied to a patient population with elimination rate constants between 0.07 1/h and 0.25 1/h, allowing a mean prediction error of 15%.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1435-1420
    Keywords: Key words ARDS ; tuberculosis ; pneumonia ; pregnancy ; Schlüsselwörter ARDS ; Tuberkulose ; Pneumonie ; Schwangerschaft
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Wir berichten über den Fall einer 17-jährigen Patientin, die in der 23. Schwangerschaftswoche an einem durch eine tuberkulöse Pneumonie verursachten „adult respiratory distress syndrome“ (ARDS) erkrankte. Nach Diagnosestellung und Einleitung einer antimykobakteriellen Chemotherapie und Steroidtherapie trat eine rasche Besserung ein, so daß die Patientin nach 5-tägiger Beatmung extubiert wurde. In der 37. Schwangerschaftswoche entband die Patientin eine Tochter, die innerhalb eines mehrwöchigen Beobachtungszeitraumes keine Tuberkulosesymptome zeigte.
    Notes: Summary We report about a 17 year old patient who survived an adult respiratory distress syndrome (ARDS) associated with tuberculous pneumonia in the 23rd week of pregnancy. After establishing the diagnosis and initiation of antituberculous and steroid treatment, the patient showed rapid improvement and was extubated after 5 days of ventilator treatment. In the 37th week of pregnancy, she delivered a daughter who showed no signs of tuberculosis after several weeks of observation.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Intensivmedizin und Notfallmedizin 37 (2000), S. 374-379 
    ISSN: 1435-1420
    Keywords: Key words Hemoptysis – pulmonary bleeding – bronchoscopy – bronchial artery embolization ; Schlüsselwörter Hämoptoe – pulmonale Blutungen – Bronchoskopie – Bronchialarterienembolisation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Massive intrapulmonale Blutungen sind ein bedrohliches Symptom, welche Patienten sofort zum Arzt führen. In dieser Situation sind die diagnostischen Möglichkeiten aus Zeitmangel beschränkt. Die Notfallversorgung ist notwendig um der lebensbedrohlichen Verlegung der Atemwege zu begegnen. Diese erfolgt nach den allgemeinen Regeln der Notfallmedizin. Zur effektiven Blutstillung muss zwischen lokalisierten und generalisierten Blutungsursachen unterschieden werden. Die Bronchoskopie ist indiziert, weil sie diese Differenzierung ermöglicht und die Blutung lokalisieren kann. Generalisierte pulmonale Blutungen sind meist durch systemische Erkrankungen bedingt. Sie werden entsprechend ihrer Pathogenese behandelt.¶   Die Bronchialarterienembolisation hat sich als effektives Verfahren zur Therapie lokalisierter Blutungen bewährt. Als ultima ratio gilt die chirurgische Resktion blutender Lungenanteile.
    Notes: Summary Massive intrapulmonary bleeding is an alarming symptom that causes the patient to see his doctor immediately. In this situation diagnostic possibilities are limited due to the lack of time. The immediate treatment of the patient is necessary due to the life threathening airway obstruction. Initial treatment is according to the principles of emergency medicine. In order to treat the hemorrhage effectively, it is essential to differentiate between localized and generalized causes. Bronchoscopy is able to differentiate these possibilities; furthermore it enables one to localize the site of the bleeding. Generalized pulmonary hemorrhage is mostly due to systemic diseases, which are treated according to the pathogenesis.¶   Bronchial artery embolization has proven to be effective in the therapy of localized pulmonary hemorrhage. Ultimately the surgical resection of bleeding parts of the lung may be indicated.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1434-4726
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The tracheo-esophageal shunt has not to be created too wide because of the danger of aspiration; but narrow shunts require high intrathoracical pressure for phonation. In seven patients a pulmonary function test was done and then the mean air flow and the esophageal pressure during phonation were measured. In four of these patients we obtained sufficient data: one patient showed a shunt resistance of 35 cm H2O/l/s which is comparable to the phonatory resistance of a normal glottis. In the three other patients resistances were found being 10–80 times higher than the normal glottal resistance. In those two patients having the lowest and the highest shunt resistance, respectively, the change of blood pressure in the pulmonary artery during phonation was recorded by cardiac catheterisation. In the patient with low resistance the mean arterial pressure increased twofold, whereas the other one showed a sixfold increase. From these observations it is concluded that phonation with a Staffieri-shunt often does not only mean a considerable respiratory load, but also a cardiovascular stress in the sense of the Valsalva-maneuver. Therefore, chronic lung and heart diseases should be regarded as contraindications against a Staffieri-shunt.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0843
    Keywords: Dexniguldipine-HCl ; Phase I trial ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Dexniguldipine-HCl is a new dihydropyridine compound that exerts selective antiproliferative activity in a variety of tumor models and, in addition, has a high potency in overcoming multidrug resistance. The purpose of this trial was to determine the toxicity and pharmacokinetics of dexniguldipine and to establish a recommended dose for phase II trials. A total of 37 patients with cancer were treated with oral dexniguldipine in increasing doses for up to 7 days. The main parameters evaluated were subjective tolerance and laboratory and cardiovascular parameters (blood pressure and ECG). Blood samples were drawn for analysis of the drug's pharmacokinetics. Dizziness and nausea were the major adverse events observed in seven patients, but episodes were generally mild and not clearly dose-related. Vomiting occurred in one patient. Hypotensive effects and orthostatic dysregulation were observed in some patients but were not considered to be dose-limiting. Therefore, no dose-limiting toxicity was found and the maximally tolerable dose could not be determined. Pharmacokinetic data showed wide interindividual variation and a dose-dependent increase in steady-state serum concentrations at doses of up to 1,000 mg daily, with no clear further increase being observed at higher doses. Consistently high concentrations were achieved with the 2,500-mg dose. Despite the lack of dose-limiting toxicity, higher doses of dexniguldipine do not appear to be useful for clinical evaluation because of the pharmacokinetics properties of the compound; therefore, 2,500 mg/day is recommended as the daily dose for phase II trials.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0843
    Keywords: Key words Dexniguldipine-HCl ; Phase I trial ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Dexniguldipine-HCl is a new dihydropyridine compound that exerts selective antiproliferative activity in a variety of tumor models and, in addition, has a high potency in overcoming multidrug resistance. The purpose of this trial was to determine the toxicity and pharmacokinetics of dexniguldipine and to establish a recommended dose for phase II trials. A total of 37 patients with cancer were treated with oral dexniguldipine in increasing doses for up to 7 days. The main parameters evaluated were subjective tolerance and laboratory and cardiovascular parameters (blood pressure and ECG). Blood samples were drawn for analysis of the drug’s pharmacokinetics. Dizziness and nausea were the major adverse events observed in seven patients, but episodes were generally mild and not clearly dose-related. Vomiting occurred in one patient. Hypotensive effects and orthostatic dysregulation were observed in some patients but were not considered to be dose-limiting. Therefore, no dose-limiting toxicity was found and the maximally tolerable dose could not be determined. Pharmacokinetic data showed wide interindividual variation and a dose-dependent increase in steady-state serum concentrations at doses of up to 1,000 mg daily, with no clear further increase being observed at higher doses. Consistently high concentrations were achieved with the 2,500-mg dose. Despite the lack of dose-limiting toxicity, higher doses of dexniguldipine do not appear to be useful for clinical evaluation because of the pharmacokinetic properties of the compound; therefore, 2,500 mg/day is recommended as the daily dose for phase II trials.
    Type of Medium: Electronic Resource
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