-
S Gläser,
T Ittermann, C Schäper,
A Obst,
M Dörr,
T Spielhagen,
S B Felix,
H Völzke,
T Bollmann,
C F Opitz,
C Warnke,
B Koch,
R Ewert
[show abstract]
[hide abstract]
ABSTRACT: The interpretation of gas exchange measured by cardiopulmonary exercise testing (CPET) depends on reliable reference values. Within the population based Study of Health in Pomerania (SHIP) CPET was assessed in 1706 volunteers. The assessment based on symptom limited exercise tests on a bicycle in a sitting position according to a modified Jones protocol. CPET was embedded in an extensive examination program. After the exclusion of active smokers and volunteers with evidence of cardiopulmonary and musculoskeletal disorders the reference population comprised 616 healthy subjects (333 women) aged 25 to 85 years. Reference equations including upper and/or lower limits based on quantile regression were assessed. All values were corrected for the most important influencing factors.This study provides reference equations for gas exchange and exercise capacity assessed within a population in Germany.
Pneumologie 12/2012;
-
[show abstract]
[hide abstract]
ABSTRACT: Ein 37-jähriger Inder wurde mit persistierendem Husten und hohem Fieber stationär aufgenommen. Umfassende Untersuchungen sicherten
die Diagnose einer Lungentuberkulose. Die kalkulierte antituberkulöse Therapie erfolgte mit Pyrazinamid, Rifampicin, Ethambutol
und Isoniazid. Obwohl die isolierten Erreger im Resistenztest sensibel waren, persistierten die Fieberschübe. Eine Resorptionsstörung
wurde immunhistochemisch ausgeschlossen. Erst im Verlauf trat unter der Standardbehandlung eine Stabilisierung ein; nach 10Wochen
bestand erstmalig kein Fieber mehr.
A 37-year-old man of Indian origin was admitted to the hospital with persistent cough and high fever. Comprehensive examination
led to the diagnosis of pulmonary tuberculosis. Although the bacilli were sensitive to the orally administered antitubercular
drugs, including pyrazinamide, rifampicin, ethambutol, and isoniazid, the fever attacks persisted. Drug malabsorption was
excluded histochemically. Under continuous antitubercular treatment, the patient’s condition was stabilized, and after 10weeks,
the fever finally disappeared.
Der Pneumologe 04/2012; 6(6):408-414.
-
[show abstract]
[hide abstract]
ABSTRACT: Vor genau 80Jahren wurde in Deutschland die erste Untersuchung mit dem Rechtsherzkatheter (RHK) durchgeführt. Anfänglich
zur Diagnostik bei Patienten mit erworbenen und angeborenen Herzfehlern genutzt, wird heute der RHK zusätzlich in der Intensivmedizin
angewendet. Trotz der Entwicklung nichtinvasiver, bildgebender Verfahren ist auch heute die Diagnosestellung einer pulmonalen
Hypertonie (PH) nur nach RHK-Diagnose akzeptiert. Während einer solchen Untersuchung wird häufig auch eine Testung der Gefäßreagibilität
durchgeführt.
Die Indikationen, technischen Besonderheiten sowie mögliche Komplikationen bei der Durchführung des RHK werden beschrieben.
Zur Interpretation der RHK-Messwerte müssen das gesamte klinische Bild des Patienten sorgfältig einbezogen und mögliche Fehlerquellen
berücksichtigt werden. Neben der Erstdiagnostik ist bei Patienten mit PH auch bei unklarer Verschlechterung der klinischen
Situation sowie bei diskrepanten Befunden aus der nichtinvasiven Diagnostik eine RHK-Untersuchung im Verlauf sinnvoll.
Eighty years ago, the first right heart catheterization (RHC) was accomplished in Germany. Initially developed to assess patients
with congenital and acquired heart defects, its spectrum of use has widened. Thus, RHC plays an important role in intensive
care medicine and cardiopulmonary surgery. Despite recent progress in noninvasive hemodynamic monitoring facilities, RHC is
still the gold standard for diagnosing pulmonary hypertension (PH). Furthermore, in this indication RHC is frequently used
to assess pulmonary vasoresponsiveness.
This overview emphasizes the indications, technical needs, and possible complications of RHC. Because RHC may be a source
of technical and interpretational errors, the obtained results need to be assessed within the clinical picture. In PH patients,
RHC does have unquestionable value in confirming the diagnosis as well as in assessing clinical worsening, and discrepancies
between noninvasive investigations and the clinical picture can be clarified.
Der Pneumologe 04/2012; 6(6):370-377.
-
S Gläser,
T Ittermann,
B Koch,
H Völzke,
H Wallaschofski,
M Nauck,
C Warnke,
C Vogelmeier,
H Schulz,
S B Felix,
R Ewert, C Schäper
[show abstract]
[hide abstract]
ABSTRACT: Although several levels of evidence have suggested an association between systemic inflammation and spirometric lung volumes, data addressing the potential interrelationship between airflow limitation and inflammatory markers are sparse and remain controversial. Potential associations between high-sensitivity C-reactive protein (hsCRP), fibrinogen and lung function were investigated in 1,466 individuals aged 25-85 yrs, representing a general population. Within this cross-sectional population, data on body plethysmography, spirometry, helium dilution and diffusing capacity of the lung for carbon monoxide (D(L,CO)) were analysed. After adjustment for potential confounding factors, such as smoking, obesity and cardiorespiratory fitness, there was an inverse association of hsCRP with forced expiratory and static lung volumes. In neither apparently healthy nor the entire population was inflammation associated with airflow limitation in central airways. In smokers only, higher hsCRP and fibrinogen were associated with an impaired D(L,CO). This study shows that higher levels of hsCRP are associated with decreased lung volumes in a general population over a wide age range. A consistent interrelationship of central airflow limitation and inflammation was not verifiable. Smoking is related to an impaired D(L,CO) in association with an increase in systemic inflammation.
European Respiratory Journal 06/2011; 39(1):29-37. · 5.89 Impact Factor
-
C Spitzer,
B Koch,
H J Grabe,
R Ewert,
S Barnow,
S B Felix,
T Ittermann,
A Obst,
H Völzke,
S Gläser, C Schäper
[show abstract]
[hide abstract]
ABSTRACT: Trauma exposure and post-traumatic stress disorder (PTSD) are associated with self-reported asthma and chronic obstructive pulmonary disease. However, these conditions have not yet been related to objective measures of lung function. 1,772 adults from the general population were assessed regarding their medical histories and spirometric lung function. Additionally, they were administered a PTSD interview, and assigned to three groups: no trauma; trauma, but no PTSD; and trauma with PTSD. Adjusting for sociodemographic, clinical and lifestyle factors, subjects with PTSD had significantly higher odds ratios for most asthma-related symptoms than PTSD-negative participants (OR 3.2-8.8). The mean ratio of forced expiratory volume in 1 s (FEV₁) to forced vital capacity (FVC) was lowest in the PTSD group and highest in those without trauma exposure. Traumatic stress was independently associated with FEV₁ and FEV₁/FVC. Participants with PTSD, compared with those without, had a significantly increased risk for airflow limitation independent of its definition (OR 4.2-7.8). This is the first study relating traumatic stress and PTSD, respectively, to objective parameters of lung function. Our findings suggest an association of trauma exposure and PTSD with airflow limitation, which may be mediated by inflammatory processes.
European Respiratory Journal 05/2011; 37(5):1068-75. · 5.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Leukotrienes, especially LTC4, are important inflammatory mediators in allergic and nonallergic inflammation of the entire airways. Of particular interest are numerous theories regarding the pathogenesis of aspirin intolerance with subsequent hyperproduction of leukotrienes and inhibition of cyclooxygenase.
To examine the influence of the cysteinyl-leukotriene receptor antagonist montelukast on clinical symptoms and inflammatory markers in nasal lavage fluid in patients with bronchial asthma and nasal polyps, and determine its dependency on aspirin sensitization.
Twenty-four patients (7 women, 17 men; median age, 55.5 years) with nasal polyps and controlled asthma (n=12 with aspirin intolerance) were treated with 10 mg montelukast once daily for 6 weeks in a blinded, placebo-controlled fashion. The placebo phase was randomly assigned 4 weeks before (n=12) or after treatment (n=12). Symptom score, rhinoendoscopy, rhinomanometry, smears for eosinophils, and nasal lavages for the determination of different mediators were performed.
Compared to placebo, there were significant improvements in the nasal symptom score and airflow limitation as well as a reduction in the inflammatory mediators in nasal lavage fluid after treatment. Furthermore, reduced eosinophils in nasal smears and peripheral blood were observed 2 and 6 weeks after treatment.
Leukotriene 1 receptor blockade led to a significant decrease in eosinophil inflammation accompanied by a reduction in other mediators such as neurokinin A and substance P in the nasal lavage fluid of patients with nasal polyps and asthma, with or without aspirin intolerance.
Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 01/2011; 21(1):51-8. · 2.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Increased end-tidal oxygen (ET-O(2)) and decreased end-tidal carbon dioxide (ET-CO(2)) gas tensions are noninvasively measurable correlates of ventilatory inefficiency, leading to increased ventilatory requirements relative to gas exchange among patients with chronic heart failure (CHF). We investigated the prognostic value of ET-O(2) and ET-CO(2) as predictors of CHF mortality.
We measured resting ET-O(2) and ET-CO(2) electrochemically in 134 patients with symptomatic CHF in the supine position. We used Kaplan-Meier analysis, Cox proportional hazard models, and receiver operating characteristic curves to test our hypothesis.
At a median follow-up of 16.5 months, 32 patients had died. ET-O(2) levels were increased (P = .001) and ET-CO(2) levels decreased (P = .002) with increased New York Heart Association class (I-IV). Survivors showed lower ET-O(2) (121 vs 118 mm Hg; P = .021) and higher ET-CO(2) (33.2 vs 32.1 mm Hg; P = .032) levels than nonsurvivors. Patients with ET-O(2) values ≥121 mm Hg and/or ET-CO(2) values <31 mm Hg had an increased risk of death with hazard ratios of 2.93 (95% confidence interval [CI], 1.43-6.01) and 2.47 (95% CI, 1.23-4.97), respectively. Kaplan-Meier estimates for follow-up mortality with ET-O(2) ≥121 mm Hg and/or ET-CO(2) <31 mm Hg were 83.8% (vs 60.1%; P = .0014) and 80.3% (vs 60.2%; P = .0061), respectively. Areas under the receiver operating characteristic curves for prediction of death with ET-O(2) and ET-CO(2) were both significant and similar to that of echocardiographic left ventricular function.
In CHF, high levels of ET-O(2) and low levels of ET-CO(2) are associated with increased mortality. We suggest that the measurements may be useful prognostic markers for risk stratification.
Transplantation Proceedings 09/2010; 42(7):2681-6. · 1.00 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recent guidelines reveal that allergic rhinitis impairs quality of life. Neuropeptides play a central role in allergy-related nasal inflammation. The objective of this study was to analyze the release of neuropeptides (substance P, neurokinin A, and vasoactive intestinal peptide) in nasal lavage and their modification by intranasal fluticasone propionate as an established therapy in patients with allergic rhinitis.
Eleven patients with proven allergic rhinitis induced by house dust mite were challenged before and after administration of fluticasone propionate nasal spray. Nasal lavage samples were collected after allergen challenge, and neuropeptides were measured using enzyme-linked immunosorbent assay. Values for histamine, protein, and human serum albumin were also recorded. Eight healthy individuals were included as nonatopic controls.
The neuropeptides investigated were detectable in nasal lavage fluid in both patients and controls. Treatment with fluticasone propionate significantly decreased clinical response to allergen challenge (P < .01) compared with the controls and led to a decrease in values for substance P, neurokinin A, vasoactive intestinal peptide, histamine release, human serum albumin, and total protein after allergen challenge (P < .01).
The demonstration of proinflammatory neuropeptides in NAL and suppression of their release after allergen challenge caused by a topical corticosteroid suggest a role for neuropeptides in allergic inflammation. Diminished release of neuropeptides induced b fluticasone propionate was accompanied by an improvement in the clinical symptoms of patients with persistent allergic rhinitis.
Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 01/2010; 20(3):214-21. · 2.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The assessment of lung function with spirometry is a frequently performed diagnostic procedure and is considered an important tool in medical monitoring of pulmonary diseases. This study aimed at establishing current reference standards, derived from a representative population sample in West Pomerania of Germany and to compare them to existing data.
Standardized spirometric function tests were performed - 1sec forced respiratory volume (FEV1) and forced vital capacity (FVC) - on 1,809 participants (885 men, 924 women) of a cross-sectional epidemiological survey, called Study of Health in Pomerania ( SHIP).
All persons with cardiac disorders, current smokers and those who were on specific medication which could influence lung functions were excluded, leaving a total of 904 healthy subjects (439 men, 465 women, aged 25-85 years. The results were analysed by quantile regression.
The study provides a representative, gender specific set of predictive equations for lung function parameters by spirometry. Comparison to existing prediction equations revealed a consistent underestimation in the current population. The results help to interpret the results of lung function tests: it is therefore recommended that the existing prediction equations be revised.
DMW - Deutsche Medizinische Wochenschrift 11/2009; 134(46):2327-32. · 0.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Allergic rhinitis, a disease that impairs quality of life, is characterized by inflammation due to an allergic reaction. Fexofenadine is a second-generation histamine receptor blocker well known for its potent interaction with this inflammatory process. The main aim of this study was to further clarify the anti-inflammatory effects exerted by fexofenadine in patients with intermittent allergic rhinitis.
Twenty patients with intermittent allergic rhinitis due to birch and mugwort pollen were enrolled. Fexofenadine was administered once a day at a dose of 120 mg. Clinical improvement was assessed by a symptom score, and nasal airway flows were measured by anterior rhinomanometry at baseline and after 2 weeks of treatment with fexofenadine. Nasal smears were tested for eosinophils and nasal lavage fluid were examined for histamine, cysteinyl leukotrienes, soluble intercellular adhesion molecule-1, eosinophil cationic protein, and albumin by enzyme-linked immunosorbent assay. All the tests were performed during the pollen season.
Fexofenadine induced a significant improvement in nasal and ocular symptoms (P < .001), nasal edema and secretion (P < .001), and nasal airway flow (P < .001). The clinical improvement was related to a significant reduction in all inflammatory mediators (P < .01 in all cases).
This study demonstrates that fexofenadine is able to mediate significant changes in different nasal lavage markers from patients with intermittent allergic rhinitis. The changes observed in the markers analyzed in both nasal secretions and serum are attributable to the anti-inflammatory effects of fexofenadine in vivo.
Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 01/2009; 19(6):459-64. · 2.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Despite recent remarkable efforts in the medical treatment options of patients with pulmonary arterial hypertension (PAH) a considerable number of patients need escalations to improve disease related symptoms and pulmonary hemodynamics. Most of the pulmonary vascular vasodilators have been approved in its potency as an initial and sole medical option. However, there is increasing scientific evidence on the reliability, safety and effectiveness of possible combinations. This paper reviews the current scientific literature about medical escalations and combination therapy in patients with PAH.
DMW - Deutsche Medizinische Wochenschrift 10/2008; 133 Suppl 6:S187-90. · 0.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cardiopulmonary exercise testing (CPET) is a widely applied clinical procedure. The aim of the present study was to acquire a comprehensive set of reference values for cardiopulmonary responses to exercise and to evaluate possible associations with sex, age and body mass index (BMI). A standardised progressive incremental exercise protocol on a cycle ergometer was applied to 1,708 volunteers of a cross-sectional epidemiologic survey, called "Study of Health in Pomerania". Individuals with cardiopulmonary disorders, or echocardiographic or lung function pathologies, were excluded. The influence of potential confounding factors, such as smoking, taking beta-blockers, hypertension, diastolic dysfunction, BMI and physical activity, were analysed for their influencing power. Reference values of CPET parameters were determined by regression analyses. Of the volunteers, 542 current smokers and obese individuals were excluded for not being representative of a healthy population. The final sample size was 534 (253 males), with age 25-80 yrs. The current study provides a representative set of reference values for CPET parameters based on age and weight. Sex and age have a significant influence on exercise parameters. While addressing the problem of a selection bias, the current study provides the first comprehensive set of reference values obtained in a large number of healthy volunteers within a population-based survey.
European Respiratory Journal 10/2008; 33(2):389-97. · 5.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Most patients (pts) with metastatic non-small cell lung cancer (NSCLC) receive either single agents or chemotherapy doublets. Recent studies have demonstrated that triple-agent therapies may improve the response rate, but are associated with significant toxicity, and frequently do not prolong survival. A sequential triple-agent schedule may combine acceptable tolerability and good efficacy. We therefore conducted a multicentre, prospectively randomized study that evaluates a sequential three-drug schedule and a platinum-free doublet regimen.
The pts with union international contre le cancer (UICC) stage IV NSCLC were randomized to one of two schedules: in arm Doc-Gem, they received gemcitabine (900 mg/m(2), 30 min infusion) on days 1 and 8, and docetaxel (75 mg/m(2), 1 h infusion) on day 1, repeated every 3 weeks up to six cycles. In arm Cis-Gem-->Doc, gemcitabine (900 mg/m(2), days 1 and 8) and cisplatin (70 mg/m(2), 1 h infusion, day 1) were given for three cycles, followed by three cycles of docetaxel (100 mg/m(2), day 1, repeated every 3 weeks).
One hundred and thirteen pts were randomized to arms Doc-Gem (55 pts) and Cis-Gem-->Doc (58 pts). With Doc-Gem, 20.4% of pts responded to the treatment whereas 31.0% responded in arm Cis-Gem-->Doc (overall response, intent-to-treat, difference not significant). The median time to progression was 3.6 months in arm Doc-Gem [95% confidence interval (CI) 1.4, 5.9] and 5.2 months in arm Cis-Gem-->Doc (95% CI 3.1, 7.3). The median survival was 8.7 months with treatment Doc-Gem (95% CI 5.7, 11.6) and 9.4 months with treatment Cis-Gem-->Doc (95% CI 7.8, 11.0). The 1-year survival rates were 34 and 35%, respectively. Mild to moderate leukopenia was frequently seen with both schedules. Other common adverse events (AE) were nausea/vomiting, thrombocytopenia, anaemia, diarrhoea, and infections. No significant differences in AEs were observed between the schedules except for nausea/vomiting, which occurred more frequently with Cis-Gem-->Doc.
The sequential therapy comprising cisplatin, gemcitabine, and docetaxel demonstrated promising tumour control whereas the platinum-free combination (docetaxel/gemcitabine) was very well tolerated. However, the schedules resulted in comparable survival to recent large trials in pts with advanced NSCLC. The present results do not justify further phase III investigation.
Cancer Chemotherapy and Pharmacology 07/2007; 60(1):143-50. · 2.83 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cerebral metastases are a frequent complication of lung cancer. They often determine patients' prognosis and need urgent therapeutic intervention. Based on histologic type, former therapies, age and performance of the patient, the number of cerebral lesions and the extracerebral tumour activity, individualized treatments are applied. For patients who suffer from non-small cell lung cancer and a single CNS lesion the best results can be achieved if they are surgically resected or receive radiosurgery. Their survival time can be markedly increased in comparison to patients who undergo whole brain irradiation. If multiple metastases are seen in CT or MRI, whole brain irradiation is the therapy to choose. Furthermore it should be initiated if small cell lung cancer metastasizes to the brain. More aggressive local treatment options appear promising, but a clear role for them has not yet been defined. Systemic chemotherapy gains more attention in the treatment of small and non-small cell lung cancer with brain metastases. How to increase the efficacy through simultaneous application of chemo- and radiotherapy is tested in current trials. This article gives an overview on clinical presentation and diagnosis of cerebral metastases in lung cancer and reviews current treatment options.
DMW - Deutsche Medizinische Wochenschrift 02/2006; 131(4):165-71. · 0.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The neurotrophins Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF) and Neurotrophin (NT)-3 are produced, stored and released by various immunological cells. The influence of NTs upon the function of these cells is described. Elevated plasma levels were found in inflammatory, autoimmune and allergic diseases with the highest levels in allergic asthma. A connection between bronchial hyper-responsiveness and serum levels has been reported.
Little is known about the influence of treatment with inhaled corticosteroids (ICS) on serum NT levels and their influence on the asthmatic state.
Eighty-seven volunteers were studied. Thirty-eight were stable allergic asthmatics with constant ICS doses, 29 were asthmatics not receiving anti-asthmatic treatment and 20 were age- and sex-matched healthy controls. Demographic and lung function data were evaluated. NT serum levels were determined by ELISA.
NGF and BDNF levels were significantly increased in untreated asthmatics compared to the control and the treated group, while NT-3 demonstrated significantly higher levels in treated asthmatics compared to healthy controls. After stabilization of untreated subjects with ICS, the NT levels decreased significantly.
These results suggest that NTs participate in allergic inflammation and asthma. Effective treatment leads to a decrease of circulating neurotrophic factors.
Clinical & Experimental Allergy 01/2002; 31(12):1906-12. · 5.03 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Background The neurotrophins Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF) and Neurotrophin (NT)-3 are produced, stored and released by various immunological cells. The influence of NTs upon the function of these cells is described. Elevated plasma levels were found in inflammatory, autoimmune and allergic diseases with the highest levels in allergic asthma. A connection between bronchial hyper-responsiveness and serum levels has been reported.Objective Little is known about the influence of treatment with inhaled corticosteroids (ICS) on serum NT levels and their influence on the asthmatic state.Methods Eighty-seven volunteers were studied. Thirty-eight were stable allergic asthmatics with constant ICS doses, 29 were asthmatics not receiving anti-asthmatic treatment and 20 were age- and sex-matched healthy controls. Demographic and lung function data were evaluated. NT serum levels were determined by ELISA.Results NGF and BDNF levels were significantly increased in untreated asthmatics compared to the control and the treated group, while NT-3 demonstrated significantly higher levels in treated asthmatics compared to healthy controls. After stabilization of untreated subjects with ICS, the NT levels decreased significantly.Conclusions These results suggest that NTs participate in allergic inflammation and asthma. Effective treatment leads to a decrease of circulating neurotrophic factors.
Clinical & Experimental Allergy 11/2001; 31(12):1906 - 1912. · 5.03 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Elevated intracranial pressure (ICP) resulting from impaired drainage of cerebrospinal fluid (CSF) causes hydrocephalus with damage to the central nervous system. Clinical symptoms of elevated intracranial pressure (ICP) in infants may be difficult to diagnose, leading to delayed treatment by shunt placement. Until now, no biochemical marker of elevated ICP has been available for clinical diagnosis and monitoring. In experimental animal models, nerve growth factor (NGF) and neurotrophin-3 (NT-3) have been shown to be produced by glial cells as an adaptive response to hypoxia. We investigated whether concentrations of NGF and NT-3 are increased in the CSF of children with hydrocephalus.
NGF was determined in CSF samples collected from 42 hydrocephalic children on 65 occasions (taps or shunt placement surgery). CSF samples obtained by lumbar puncture from 22 children with suspected, but unconfirmed bacterial infection served as controls. Analysis was performed using ELISA techniques.
NGF concentrations in hydrocephalic children were over 50-fold increased compared to controls (median 225 vs 4 pg/mL, p < 0.0001). NT-3 was detectable (> 1 pg/mL) in 14/31 hydrocephalus samples at 2-51 pg/mL but in none of 11 control samples (p = 0.007).
NGF and NT-3 concentrations are increased in children with hydrocephalus. This may represent an adaptive response of the brain to elevated ICP.
BMC Pediatrics 01/2001; 1:2. · 1.88 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In a recent study mast cell heparin proteoglycan (HepPG) of a cell line derived from a mouse mastocytoma was isolated. Glycosaminoglycans proved to be an initiating surface for starting contact activation and could explain kinin generation present in allergic reactions. It is the aim of the present study to prove that HepPG or glycosaminoglycan derived from human mast cells is also capable of acting as a physiologic macromolecule and to induce contact activation.
HepPG molecules were isolated by anionic column chromatography. Their ability to accelerate reciprocal activation of factor XII was investigated by spectrophotometry. The anticoagulant effect was demonstrated by an increase in partial thromboplastin time. HPLC was performed to correlate these effects with molecular weight (MW).
The isolated heparin showed high contact-activating and anticoagulant potency. Both actions were suppressed by incubation with heparinase I. The maximum contact activation peak appeared at a lower MW than the anticoagulant effect.
These in vitro results explain the results of in vivo allergen challenge studies where a high degree of kinin generation occurs. Heparin derived from human mast cells therefore seems to represent the physiological macromolecule capable of activating the contact system and could be a missing link between cellular and humoral responses in allergic reactions.
International Archives of Allergy and Immunology 01/2000; 120(4):310-6. · 2.40 Impact Factor
-
Allergy 12/1998; 53(11):1023-42. · 6.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Neutral endopeptidase 24.11 (NEP) degrades vasoactive peptides, including natriuretic peptides, kinins, angiotensins, and endothelins. It contributes to the regulation of vascular tone and body fluid homeostasis. In the present study the expression of NEP was investigated in cultured human smooth muscle cells derived from umbilical veins (HSMC) and human coronary arteries (HCSMC). A constitutive NEP expression was found in growing and starved smooth muscle cells and was about 4 fold higher than in endothelial cells derived from umbilical veins. Treatment of smooth muscle cells with dexamethasone (0.01-0.1 microM Dex) and with the protein kinase C activator, phorbol myristate acetate (0.1 microM PMA), increased NEP mRNA by 3-4 fold and two fold, respectively. Dexamethasone (0.1 microM) and prednisolone (0.1 microM) increased protein concentrations of NEP and NEP-activity after 3 days and continued to increase at 5 days, whereas PMA induced maximal increase of NEP concentrations after 48 hours. The effect of dexamethasone was concentration-dependent and was completely abolished by cycloheximide (10 microM), a protein synthesis inhibitor. The effect of PMA on NEP protein was completely blocked by protein kinase C inhibitors, calphostin C and H7 (both 10 microM). NEP 24.11 is constitutively expressed in human smooth muscle cells from umbilical veins and coronary arteries and is upregulated by glucocorticoids and by protein kinase C activation in these cells.
Archiv für Kreislaufforschung 02/1998; 93(1):11-7. · 7.35 Impact Factor
