Biomedical subjects

Johann Christian Virchow

Publications and source records attributed to Johann Christian Virchow.

9 recordsLinked to original sources

PubMed2006

Differential expression of the neurotrophin receptors p75NTR, TrkA, TrkB and TrkC in human peripheral blood mononuclear cells.

Neurotrophins are involved in the pathogenesis of allergic asthma. In addition to their influence on afferent sensory nerves within the lung, it has been shown in the last years that these factors modulate allergic airway inflammation. The knowledge about their immunomodulatory roles on diverse subsets of immune cells is still fragmentary and incomplete. Since neurotrophin receptor surface expression is essential for neurotrophin action, the aim of our study was to systematically investigate the expression pattern of the low affinity pan neurotrophin receptor p75NTR as well as the high-affinity receptors TrkA, TrkB and TrkC in human peripheral blood mononuclear cells. Our results show that each of the receptors has an individual expression pattern in diverse immune cell subtypes. However, there were no differences in neurotrophin receptor expression in healthy controls and patients with allergies.

Adult↗

PubMed2006

Randomized, multicenter, open-label phase II study of gemcitabine plus single-dose versus split-dose carboplatin in the treatment of patients with advanced-stage non-small-cell lung cancer.

BACKGROUND: Gemcitabine/carboplatin is a convenient and effective treatment for advanced-stage non-small-cell lung cancer (NSCLC), but modification of the schedule to diminish thrombocytopenia is worthwhile. PATIENTS AND METHODS: One hundred fifty-eight chemotherapy-naive patients with stage IIIB/IV NSCLC were randomized from 15 centers in Germany to receive gemcitabine 1250 mg/m(2) on days 1 and 8 plus carboplatin area under the curve 5 on day 1 (arm A) or carboplatin area under the curve 2.5 on days 1 and 8 (arm B), every 21 days for 4 cycles. RESULTS: The 2 arms (A vs. B) were well balanced with regard to patient baseline characteristics: stage IV 72.5% versus 69%, median Eastern Cooperative Oncology Group performance status 1 versus 1. The incidence of grade 3/4 hematologic toxicity was as follows (percentage of patients in arm A vs. B): leukopenia 37.5% versus 27% (P = 0.075), granulocytopenia 36% versus 36%, and thrombocytopenia 51% versus 35% (P = 0.017). Nonhematologic toxicity was modest and comparable with both schedules. The overall response rate was 46% versus 36% (P = 0.12), and 24% versus 42% had stable disease. Median progression-free survival (5.8 months vs. 6.1 months) and overall survival (11.7 months vs. 10.7 months) were not significantly different between arms A and B. CONCLUSION: Splitting the dose of carboplatin between days 1 and 8 on the same days as gemcitabine results in a significantly decreased incidence of severe thrombocytopenia, without compromising the activity of the combination.

Adult↗

PubMed2005

Neurotrophins in murine viscera: a dynamic pattern from birth to adulthood.

There is growing evidence that target-derived neurotrophins regulate the function of visceral neurons after birth. However, the postnatal profile of neurotrophin supply from internal organs is poorly described. In this study, we compared neurotrophin concentrations in lysates of murine peripheral target tissues (lung, heart, liver, colon, spleen, thymus, kidney and urinary bladder) at different time points after birth. In most organs, there was a decrease of neurotrophin concentrations in the first weeks after birth. In contrast, there were characteristic increases of specific neurotrophins during adolescence or adulthood. These increases were found for nerve growth factor (NGF) in the heart, thymus, kidney and liver, for brain-derived neurotrophic factor (BDNF) in the lung, and for neurotrophin-3 (NT-3) in the colon. In conclusion, we show that neurotrophins display a very differential and dynamic profile in internal organs after birth.

Aging↗

PubMed2005

The impact of age, weight and gender on BDNF levels in human platelets and plasma.

Brain-derived neurotrophic factor (BDNF) is a key mediator of neuronal plasticity in the adult. BDNF is known to be stored in human platelets and to circulate in plasma, but the regulation and function of BDNF in peripheral blood is still poorly understood. In this prospective study, we have examined 140 healthy, non-allergic adults (20-60 years old) to elucidate the impact of age and physical parameters on BDNF levels in human platelets and plasma. There was a wide concentration range of BDNF in serum (median: 22.6 ng/ml), platelets (median: 92.7 pg/10(6) platelets) and plasma (median: 92.5 pg/ml). BDNF levels in plasma decreased significantly with increasing age or weight, whereas platelet levels did not. When matched for weight, there were no significant gender differences regarding BDNF plasma levels. However, women displayed significantly lower platelet BDNF levels than men. In addition, platelet BDNF levels changed during the menstrual cycle. In conclusion, we demonstrate that parameters such as age or gender have a specific impact on stored and circulating BDNF levels in peripheral blood.

Adult↗

PubMed2005

Comparison of volume- and pressure-limited NPPV at night: a prospective randomized cross-over trial.

Both pressure- and volume-limited non-invasive positive pressure ventilation (NPPV) have been used in patients with chronic respiratory failure. The aim of the present study was to compare the efficacy of ventilation during nocturnal volume- and pressure-limited NPPV. Fifteen patients (nine COPD, six non-COPD) were randomly assigned to receive either volume-limited or pressure-limited NPPV and were switched to the complementary mode after 6 weeks. Ten patients (five COPD, five non-COPD) completed the study. PaCO2 during sleep comparably decreased from 54.6+/-8.0 to 46.2+/-6.1 mmHg during volume-limited NPPV (P<0.05), and to 46.5+/-6.4 mmHg during pressure-limited NPPV (P<0.05). Improvements in sleep quality assessed by polysomnography were comparable, but less gastrointestinal side effects were reported for pressure-limited NPPV (P<0.05). Using a pneumotachograph the variance of inspiratory volumes was lower, but the variance of peak inspiratory pressures was higher during volume-limited NPPV compared to pressure-limited NPPV. Substantial leak volumes which accounted for 57% (volume-limited NPPV) and for 58% (pressure-limited NPPV) of the applied inspiratory volume were independent from the mode of ventilation. In conclusion, nocturnal volume- and pressure-limited NPPV have similar effects on gas exchange and sleep quality in patients with hypercapnic chronic respiratory failure, but volume-limited NPPV is associated with more gastrointestinal side effects.

Adult↗

PubMed2005

Outcome of patients with stable COPD receiving controlled noninvasive positive pressure ventilation aimed at a maximal reduction of Pa(CO2).

STUDY OBJECTIVES: The role of noninvasive positive pressure ventilation (NPPV) has been well established in the treatment of acute hypercapnic respiratory failure due to COPD. However, evidence for a sustained improvement in blood gas levels and survival in patients with stable hypercapnic COPD following NPPV is still lacking. There is concern that this might be due to low inspiratory pressures of < 18 cm H2O used in previous studies, which thereby did not achieve a reduction of Pa(CO2). Therefore, the 2-year survival and changes in lung function and blood gas levels were analyzed in patients with stable hypercapnic COPD in whom controlled pressure-limited NPPV was titrated to achieve a maximal improvement in Pa(CO2). DESIGN: Retrospective study between March 1997 and September 2003. SETTING: General ward of a university hospital. PATIENTS: Thirty-four consecutive patients with stable (mean pH 7.40 +/- 0.03) hypercapnic COPD (mean age, 63.4 +/- 9.7 years [+/- SD]; mean body mass index, 28.3 +/- 7.3 kg/m2). MEASUREMENTS AND RESULTS: Daytime Pa(CO2) during spontaneous breathing decreased by 6.9 +/- 8.0 (95% confidence interval, - 9.9 to - 3.9), from 53.3 +/- 4.8 to 46.4 +/- 7.0 mm Hg (p < 0.001); while daytime Pa(O2) increased by 5.8 +/- 9.4 (95% confidence interval, 2.3 to 9.3), from 51.7 +/- 8.8 to 57.5 +/- 9.3 mm Hg (p = 0.002); and FEV1 increased by 0.14 +/- 0.16 (95% confidence interval, 0.08 to 0.20), from 1.03 +/- 0.54 to 1.17 +/- 0.59 L (p < 0.001) after 2 months of NPPV. This was achieved with mean inspiratory pressures of 27.7 +/- 5.9 cm H2O (range, 17 to 40 cm H2O) at a mean respiratory rate of 20.8 +/- 2.5 breaths/min (range, 14 to 24 breaths/min). The 2-year survival rate was 86%. CONCLUSIONS: Controlled NPPV using a mean inspiratory pressure of 28 cm H2O is well tolerated over longer periods and can improve blood gas levels and lung function. Prospective, randomized controlled trials of high-intensity NPPV are required to evaluate its role in patients with stable hypercapnic COPD.

Adult↗

PubMed2004

Brain-derived neurotrophic factor in platelets and airflow limitation in asthma.

Brain-derived neurotrophic factor (BDNF), a key mediator of neuronal plasticity, contributes to airway obstruction and hyperresponsiveness in a model of allergic asthma. BDNF is stored in human platelets and circulates in human plasma, but the significance of BDNF in this compartment is poorly understood. We investigated the relationship between platelet and plasma BDNF levels and pulmonary function in a cohort of 26 adult patients with recently diagnosed allergic asthma. BDNF levels in serum, platelets, and plasma were significantly increased in participants with asthma, as compared with 26 age- and sex-matched control subjects. In steroid-naive patients, but not in patients using inhaled corticosteroids, enhanced platelet BDNF levels correlated with parameters of airway obstruction and airway hyperresponsiveness to histamine. Experiments with activated peripheral blood mononuclear cells revealed that corticosteroids such as fluticasone effectively suppress BDNF secretion. In conclusion, we demonstrate that enhanced platelet BDNF is associated with airflow limitation and airway hyperresponsiveness in asthma. In addition, we provide evidence that corticosteroids suppress BDNF production by activated immune cells.

Adult↗

PubMed2003

The neurotrophins nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 are survival and activation factors for eosinophils in patients with allergic bronchial asthma.

Neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and NT-4) have been observed in elevated concentrations in allergic diseases. Neurotrophin levels are up-regulated endobronchially after allergen challenge. This coincides with an influx of activated eosinophils into the bronchial lumen. These eosinophils have an increased viability and CD69 expression 18 h after segmental allergen provocation (SAP) which is not present in peripheral blood. To investigate whether these observations are related we studied the influence of neurotrophins on eosinophil function in allergic asthma. Incubation with NGF, BDNF, NT-3, or NT-4 caused a significant increase in the viability and CD69 expression of isolated eosinophils from bronchoalveolar lavage fluid (BALF) but not from peripheral blood, suggesting a unique sensitivity of endobronchial eosinophils to neurotrophins. To elucidate the underlying mechanisms expression of the neurotrophin receptors p75NTR, trkA, trkB, and trkC on eosinophils was analyzed by RT-PCR and immunocytology. After SAP expression of all neurotrophin receptors was markedly elevated on eosinophils from BALF. Our findings suggest that neurotrophin-mediated activation of bronchial eosinophils might play a role in the regulation of eosinophilic inflammation in allergic asthma.

Adult↗

PubMed2002

Weaning from mechanical ventilation by long-term nasal positive pressure ventilation in two patients with acute respiratory distress syndrome associated with pneumococcal sepsis.

Only few data concerning weaning by nasal positive pressure ventilation (NPPV) are available, and successful weaning by using NPPV in patients with acute respiratory distress syndrome (ARDS) and severe complications has not yet been described. Two cases with ARDS and both preexisting thoracopulmonary disease (infundibulum abnormality and suspected COPD) and associated complications (recurrent sepsis, acute renal failure, need for lobectomy, severe malnutrition) could not be weaned by invasive ventilatory techniques. Both patients presented with rapid shallow breathing and PaCO(2) values >60 mm Hg during intermittent trials of spontaneous breathing, although the primary pathology and associated complications had been resolved. Patients were successfully adapted on NPPV in a stepwise approach after 93 days and 67 days of invasive ventilation. In one patient withdrawal from NPPV was possible after 2 months. In the other patient the duration of daily ventilation could be significantly reduced from 18 to 6 h/day after 9 months on NPPV. Therefore, patients with ARDS who cannot be weaned by invasive ventilatory strategies might be removed successfully from invasive mechanical ventilation by using NPPV even when there are preexisting thoracopulmonary disease and major complications during invasive ventilation.

Adult↗