[Linguistic Validation of the "German Lung Fibrosis Health Related Quality of Life Questionnaire"]. / Sprachliche Validierung des Fibrose-Fragebogens zur Erfassung der Lebensqualität bei Patienten mit idiopathischer Lungenfibrose und idiopathischer nichtspezifischer interstitieller Pneumonie.

Health status and quality of life are impaired in patients with idiopathic pulmonary fibrosis (IPF) and idiopathic non-specific interstitial fibrosis (iNSIP). In Germany exists only the K-BILD questionnaire for patients with ILD 1 in a professional translation by Kreuter et al. 2 This questionnaire focuses on the main problems in patients with progressive lung fibrosis in a limited manner. Therefore a new quality of life questionnaire for patients with idiopathic pulmonary fibrosis was developed and linguistically validated. METHODS: The linguistic validation of our questionnaire was carried out in a multistage process in collaboration with the developer of the questionnaire and bilingual, professional translators. Review by the developers and back translations as well as clinical assessment by IPF- and iNSIP-patients ensured that the translated questionnaire reflected the intention of the original English version of our questionnaire.Cross-validation was carried out with the St. Georges Respiratory Questionnaire (SGRQ). RESULTS: The new questionnaire concerning the health status was composed in English and German language. The questions cover five scales (sensitivity, selectivity and symptoms like breathlessness and cough and a visual analog scale on general health status) with 23 items. CONCLUSIONS: The results show that the FFB maps the special needs of the patients with IPF and iNSIP well and can support clinical and scientific questions and can be helpful in monitoring the clinical course.

[Pulmonary hypertension due to chronic lung disease: Recommendations of the Cologne Consensus Conference 2016]. / Pulmonale Hypertonie bei Lungenkrankheiten: Empfehlungen der Kölner Konsensus-Konferenz 2016.

The 2015 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) associated with chronic lung disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, sGC stimulators) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH. This recommendation, however, is not always in agreement with medical ethics as physicians feel sometimes inclined to treat other form of PH which may affect quality of life and survival of these patients in a similar manner. To this end, it is crucial to consider the severity of both PH and the underlying lung disease. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany, to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. Several working groups were initiated, one of which was dedicated to the diagnosis and treatment of PH in patients with chronic lung disease. The recommendations of this working group are summarized in the present paper.

[Pulmonary hypertension due to chronic lung disease. Recommendations of the Cologne Consensus Conference 2010]. / Pulmonale Hypertonie bei chronischen Lungenerkrankungen. Empfehlungen der Kölner Konsensus-Konferenz 2010.

The 2009 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) in chronic lung disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists and phosphodiesterase-5 inhibitors) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH. This recommendation, however, is not always in agreement with medical ethics as physicians feel sometimes inclined to treat other form of pulmonary hypertension which may affect quality of life and survival of these patients in a similar manner. In June 2010, a group of German experts met in Cologne, Germany, to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. The conference was sponsored by the German Society of Cardiology, the German Society of Respiratory Medicine and the German Society of Pediatric Cardiology. One of the working groups was dedicated to the diagnosis and treatment of PH in patients with chronic lung disease. The recommendations of this working group are summarized in the present paper.

Luteolin protects rat PC12 and C6 cells against MPP+ induced toxicity via an ERK dependent Keap1-Nrf2-ARE pathway.

Oxidative stress is central to neuronal damage in neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. In consequence, activation of the cerebral oxidative stress defence is considered as a promising strategy of therapeutic intervention. Here we demonstrate that the flavone luteolin confers neuroprotection against oxidative stress via activation of the nuclear factor erythroid-2-related factor 2 (Nrf2), a transcription factor central to the maintenance of the cellular redox homeostasis. Luteolin protects rat neural PC12 and glial C6 cells from N-methyl-4-phenyl-pyridinium (MPP+) induced toxicity in vitro and effectively activates Nrf2 as shown by ARE-reporter gene assays. This protection critically depends on the activation of Nrf2 since downregulation of Nrf2 by shRNA completely abrogates the protection of luteolin in vitro. Furthermore, the neuroprotective effect of luteolin is abolished by the inhibition of the luteolin-induced ERK1/2-activation. Our results highlight the relevance of Nrf2 for neural cell survival conferred by flavones. In particular, we identified luteolin as a promising lead for the search of orally available, blood brain barrier permeable compounds to support the therapy of neurodegenerative disorders.

[Endoscopic ultrasound-guided fine-needle aspiration in pulmonary medicine]. / Endosonographisch gesteuerte Feinnadelpunktion in der pneumologischen Diagnostik.

Endoscopic ultrasound-guided fine-needle aspiration has significantly increased the capacity of pulmonary diagnostic procedures. Since this method was introduced, 1212 examinations have been performed at two centres of pulmonary medicine. Data on indications, procedures, findings, diagnostic yield and complications have been recorded. This paper describes the experiences thus gained regarding the possibilities and limitations of the method and assesses the current significance of the technique in pulmonary medicine according to previous studies. In primary diagnosis of mediastinal tissue alterations and in staging of malignant diseases the method offers a low-complication diagnostic measure which has a seminal impact on therapy in many cases, even though in daily practise the diagnostic accuracy of published studies is not always attained.

Prevalence of respiratory symptoms, bronchial hyperresponsiveness and atopy among adults: west and east Germany.

The prevalence of respiratory symptoms, atopic sensitization and bronchial hyperresponsiveness was compared in a random sample of adults, 20-44 yrs of age, in two cities in West and East Germany, Hamburg and Erfurt, respectively. There were much higher levels of outdoor air pollution due to sulphur dioxide and suspended particulates in Erfurt, and major differences in living conditions during the last 40 yrs. Within the European Respiratory Health Survey, a short questionnaire was answered by 3,156 (80% response rate) subjects in Hamburg and 3,272 (74%) in Erfurt. A subset of responders to the short questionnaire completed a long questionnaire, spirometry, methacholine or bronchodilator test, skin test, and total and specific immunoglobulin E (IgE) measurements, with a total number of 1,159 participants in Hamburg and 731 in Erfurt. Six out of 8 questions on respiratory symptoms and diagnoses were answered in the affirmative more frequently in Hamburg than in Erfurt. In Hamburg, mean forced expiratory volume in one second (FEV1)% of predicted was 105 vs 107% in Erfurt (p < 0.0001), and bronchial hyperresponsiveness was more frequently observed in Hamburg than in Erfurt (25 vs 19%; p < 0.05). Atopic sensitization was more prevalent in Hamburg than in Erfurt regarding the results of skin tests against grass pollen (24 vs 19%; p < 0.05), birch pollen (19 vs 8%; p < 0.0005), cat (10 vs 2%; p < 0.0005), and Dermatophagoides pteronyssinus (14 vs 10%; p < 0.05). This was reflected by the prevalences of positive specific IgE values, which were higher in Hamburg than in Erfurt for grass (26 vs 20%; p < 0.05), birch (20 vs 10%; p < 0.0005) and cat (12 vs 8%; p < 0.05). In Hamburg, compared to Erfurt, there was: a lower mean number of siblings (p < 0.005); a higher degree of childhood and current exposure to environmental tobacco smoke (p < 0.005); and a higher frequency of fitted carpets and reported mould or mildew inside the house (p < 0.005). Therefore, these data may support the hypothesis that childhood factors and exposure to indoor allergens and irritants may have been more relevant for the development of asthma and atopy than the potential long-term exposure to high concentrations of sulphur dioxide and particulate matter.

Proteolysis of IGFBPs by cathepsin D in vitro and in cathepsin D-deficient mice.

Affinity-purified lysosomal protease cathepsin D cleaved recombinant human IGFBP-1 to -5 in fragments of defined sizes, while IGFBP-6 was not degraded. To assess the role of cathepsin D for proteolytic processing of IGFBP in vivo, serum from cathepsin D-deficient mice and conditioned media from cathepsin D-deficient fibroblasts and organ explants were analyzed. No differences for the pattern and level of IGFBPs were detected. When conditioned media from fibroblasts were incubated at acid pH, proteolysis of IGFBP-1 and -4 was observed only in media derived from cathepsin D-expressing cells. Additional experiments showed that the proteolysis of IGFBP-4 is mediated by cathepsin D and not by a protease activated by cathepsin D. The IGFBP-4 degrading activities in media from organ explants from cathepsin D-deficient mice were found to be sensitive to inhibitors of aspartyl and cysteine proteases. The data indicate that different classes of acid pH-dependent proteases can contribute to the regulation of IGFBP-4 abundance.

Delayed recovery from post-thyroidectomy hypoparathyroidism: a case report.

Thirteen hours after a subtotal thyroidectomy was performed for hyperthyroidism, a patient developed carpopedal spasms, parathesias and hypocalcemia to 6.9 mg/dL. After initial stabilization with intravenous calcium administration, oral calcium carbonate and calcitriol were required. Ten months postoperatively serum calcium levels rose and supplementation was gradually discontinued. The serum parathyroid hormone (PTH) level was 1.0 pg/mL on the second postoperative day and levels were undetectable despite sensitive testing 3 months later (normal 10-65 pg/mL). Two years after surgery, the PTH level has increased to 36 pg/mL, but remains relatively low considering the patient's continued mild hypocalcemia. To our knowledge, there has been no previously reported case of long-term post-thyroidectomy hypocalcemia documenting undetectable parathyroid function and subsequent spontaneous improvement. This case suggests that delayed recovery of parathyroid function and discontinuation of vitamin D and calcium supplementation may be possible in some post-thyroidectomy patients with hypocalcemia due to severe hypoparathyroidism.

Acute adrenal insufficiency presenting as shock after trauma and surgery: three cases and review of the literature.

Profound nonhemorrhagic shock developed in one postoperative and two trauma patients. Cardiovascular collapse was characterized by severe hypotension (systolic blood pressure less than 80 mm Hg), hyperdynamic cardiac indices (CI greater than 4 L/min/m2), low systemic vascular resistance (SVR less than 500 dyne.sec/cm5.m2), and multiple organ failure. Sepsis was not found by culturing of specimens or visual inspection at laparotomy. Screening cortisol levels were low (less than 2 micrograms/dL in two patients) and did not respond appropriately to synthetic ACTH (cosyntropin) challenge. Administration of exogenous glucocorticoids promptly and dramatically reversed shock and organ failure in two patients. Oral glucocorticoid and mineralocorticoid supplementation were required at hospital discharge. Acute adrenal insufficiency is rare after trauma, but may produce life-threatening cardiovascular collapse, mimicking the "septic" shock state. Cosyntropin stimulation testing confirms the diagnosis and is accurate in traumatized patients. Outcome is dependent upon early recognition and exogenous glucocorticoid administration. Appropriate endocrine evaluation prevents unnecessary use of steroids in a population of trauma patients who are already in a state of immunosuppression.

Increased plasma membrane fluidity and decreased receptor availability of nonmuscle cells in myotonic dystrophy.

Plasma membrane fluidity of intact nonmuscle cells from patients with myotonic dystrophy (MyD) was determined by fluorescence anisotropy measurements. Anisotropy values of the probe diphenylhexatriene were decreased in patient mononuclear cells (0.163 +/- 0.017, n = 13) versus controls (0.181 +/- 0.013, n = 13, P less than 0.01) and in patient platelets (0.087 +/- 0.017, n = 9) versus controls (0.137 +/- 0.015, n = 9, P less than 0.001) indicating increased plasma membrane fluidity in patient nonmuscle cells. Vasopressin plasma concentrations were increased in patients (7.4 +/- 2.1 pg/ml, n = 12) versus controls (4.5 +/- 1.4 pg/ml, n = 22, P less than 0.0005), whereas serum osmolality was normal. These data are compatible with a decreased vasopressin sensitivity in MyD patients. Specific binding of 125I-labelled vasoactive intestinal peptide (VIP) was decreased in patient mononuclear cells (2.9 +/- 0.9%/10(6) cells, n = 8) versus controls (5.2 +/- 1.6%/10(6) cells, n = 9, P less than 0.005) and receptor affinity for VIP was decreased in patient mononuclear cells (Kd = 0.26 +/- 0.05 nM, n = 8) versus controls (Kd = 0.19 +/- 0.02 nM, n = 9, P less than 0.005). In nonmuscle cells of MyD patients, increased membrane fluidity correlated with decreased receptor availability. This might explain the various endocrine defects described in MyD patients.