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Biomarkers for pulmonary manifestations in systemic lupus erythematosus (SLE) are missing. Plasma samples of nine SLE patients with known pulmonary involvement (SLEpulm) and nine SLE patients without pulmonary involvement (SLE) were tested by multiplex microarray analysis for various cyto- and chemokines. Significantly decreased lung function paramters for forced vital capacity (FVC), total lung capacity (TLC), diffusion capacity for carbon monoxide (DLCO) and diffusion of CO corrected on lung volume (KLCO) were observed in SLEpulm as compared to SLE patients. CC chemokine ligand 21 (CCL21) and interferon gamma-induced protein 10 (IP-10) levels were significantly higher in SLEpulm, than in patients without pulmonary manifestations. CCL21 correlated negatively with DLCO (r=-0.73; p<0.01) and KLCO (r=-0.62; p<0.01), while IP-10 with FVC and forced expiratory volume one second. Receiver Operating Characteristics (ROC) analysis confirmed high sensitivity and specificity for the separation of SLE patients with and without pulmonary involvement for the chemokines CCL21 (Area Under Curve (AUC): 0.85; sensitivity%: 88.90; specificity%: 75.00; p<0.01) and IP-10 (AUC: 0.82; sensitivity%: 66.67, specificity%: 100; p<0.01). Pleuropulmonary manifestations in SLE patients associated with lung functional and DLCO/KLCO changes and were associated with significant increase in CCL21 and IP-10. These chemokines might serve as potential biomarkers of lung involvement in SLE patients. [ABSTRACT FROM AUTHOR]

Little is known about the influence of (impaired) neurodevelopment on cognitive aging. We here used a mouse model for tuberous sclerosis (TS) carrying a heterozygous deletion of the Tsc2 gene. Loss of Tsc2 function leads to mTOR hyperactivity in mice and patients. In a longitudinal behavioral analysis, we found premature decline of hippocampus‐based cognitive functions together with a significant reduction of immediate early gene (IEG) expression. While we did not detect any morphological changes of hippocampal projections and synaptic contacts, molecular markers of neurodegeneration were increased and the mTOR signaling cascade was downregulated in hippocampal synaptosomes. Injection of IGF2, a molecule that induces mTOR signaling, could fully rescue cognitive impairment and IEG expression in aging Tsc2+/− animals. This data suggests that TS is an exhausting disease that causes erosion of the mTOR pathway over time and IGF2 is a promising avenue for treating age‐related degeneration in mTORopathies. [ABSTRACT FROM AUTHOR]

Background: Induced pluripotent stem cell (iPSC) based neuronal differentiation is valuable for studying neuropsychiatric disorders and pharmacological mechanisms at the cellular level. We aimed to examine the effects of typical and atypical antipsychotics on human iPSC-derived neural progenitor cells (NPCs)., Methods: Proliferation and neurite outgrowth were measured by live cell imaging, and gene expression levels related to neuronal identity were analyzed by RT-QPCR and immunocytochemistry during differentiation into hippocampal dentate gyrus granule cells following treatment of low- and high-dose antipsychotics (haloperidol, olanzapine, and risperidone)., Results: Antipsychotics did not modify the growth properties of NPCs after 3 days of treatment. However, the characteristics of neurite outgrowth changed significantly in response to haloperidol and olanzapine. After three weeks of differentiation, mRNA expression levels of the selected neuronal markers increased (except for MAP2), while antipsychotics caused only subtle changes. Additionally, we found no changes in MAP2 or GFAP protein expression levels as a result of antipsychotic treatment., Conclusions: Altogether, antipsychotic medications promoted neurogenesis in vitro by influencing neurite outgrowth rather than changing cell survival or gene expression. This study provides insights into the effects of antipsychotics on neuronal differentiation and highlights the importance of considering neurite outgrowth as a potential target of action.

Introduction: Morbidity and mortality due to chronic obstructive pulmonary disease (COPD) are on the rise worldwide. The cornerstone of treatment is maintenance inhaled therapy and the patients’ good treatment adherence. Objective: To determine epidemiological and treatment characteristics of patients treated with COPD in Hungary. Methods: Using data from the National Health Insurance Fund, we recruited patients under maintenance inhaled therapy due to COPD between 2011 and 2019 (aged >40 years, who filled in at least one prescription of a maintenance inhaled drug for ICD (International Classification of Diseases) code J44, which was followed by two further prescriptions within 1 year). Data of patients were analysed every year after inclusion. Findings on age, sex, inhaled therapies, and the use of retard oral theophylline were compared among the years (chi2 test). Results: In total, 227,251 patients were included (2011–2019: 81,308–160,241 patients/year). In 2011, most patients were >70 years of age and males, while in 2019, most patients were 60–69 years old and females. The proportion of patients filling in a prescription for mono-bronchodilators or inhaled corticosteroids decreased in the observational period, while dual bronchodilators became available, and their use gradually increased. The adherence to maintenance inhaled therapies was good (>180 days/year) only in approximately half of the population (51.6% in 2019). The number of patients filling in prescriptions for oral theophylline did not decline in the observation period (32% in 2019). Discussion: Between 2011 and 2019, the number of COPD patients on maintenance inhaled therapy did not reach that of the registered patients. Adherence to maintenance inhaled treatment is inadequate in a significant portion of patients. The rate of patients taking oral theophylline is high. Conclusion: Improvement of adherence to maintenance inhaled therapies is essential for a better prognosis of COPD in Hungary. Orv Hetil. 2024; 165(9): 338–345.

Background: Schizophrenia (SCZ) is a severe neuropsychiatric disorder of complex, poorly understood etiology, associated with both genetic and environmental factors. De novo mutations (DNMs) represent a new source of genetic variation in SCZ, however, in most cases their biological significance remains unclear. We sought to investigate molecular disease pathways connected to DNMs in SCZ by combining human induced pluripotent stem cell (hiPSC) based disease modeling and CRISPR-based genome editing., Methods: We selected a SCZ case-parent trio with the case individual carrying a potentially disease causing 1495C > T nonsense DNM in the zinc finger MYND domain-containing protein 11 (ZMYND11), a gene implicated in biological processes relevant for SCZ. In the patient-derived hiPSC line the mutation was corrected using CRISPR, while monoallelic or biallelic frameshift mutations were introduced into a control hiPSC line. Isogenic cell lines were differentiated into hippocampal neuronal progenitor cells (NPCs) and functionally active dentate gyrus granule cells (DGGCs). Immunofluorescence microscopy and RNA sequencing were used to test for morphological and transcriptomic differences at NPC and DGCC stages. Functionality of neurons was investigated using calcium-imaging and multi-electrode array measurements., Results: Morphology in the mutant hippocampal NPCs and neurons was preserved, however, we detected significant transcriptomic and functional alterations. RNA sequencing showed massive upregulation of neuronal differentiation genes, and downregulation of cell adhesion genes. Decreased reactivity to glutamate was demonstrated by calcium-imaging., Conclusions: Our findings lend support to the involvement of glutamatergic dysregulation in the pathogenesis of SCZ. This approach represents a powerful model system for precision psychiatry and pharmacological research., Competing Interests: Declaration of competing interest The authors have no competing financial interests to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Insulin and insulin-like growth factor 1 (IGF1) signalling play a central role in the development and maintenance of neurons in the brain, and human neurodevelopmental as well as neuropsychiatric disorders have been linked to impaired insulin and IGF1 signalling. This review focuses on the impairments of the insulin and IGF1 signalling cascade in the context of neurodevelopmental and neuropsychiatric disorders, based on evidence from human neuronal cell models. Clear evidence was obtained for impaired insulin and IGF1 receptor downstream signalling in neurodevelopmental disorders, while the evidence for its role in neuropsychiatric disorders was less substantial. Human neuronal model systems can greatly add to our knowledge about insulin/IGF1 signalling in the brain, its role in restoring dendritic maturity, and complement results from clinical studies and animal models. Moreover, they represent a useful model for the development of new therapeutic strategies. Further research is needed to systematically investigate the exact role of the insulin/IGF1 signalling cascades in neurodevelopmental and neuropsychiatric disorders, and to elucidate the respective therapeutic implications., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Solid organ transplant (SOT) recipients represent a vulnerable patient population and are of high risk for airborne viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Treatment of COVID-19 is still challenging, as no proven therapeutic regimen is available for immunocompromised patients. Our aim was to evaluate the efficacy and safety of remdesivir (RDV) therapy in infected hospitalized SOT patients. All transplanted recipients (N = 25; lung: 19; kidney: 3, liver: 2, heart: 1) who needed hospital care were reviewed in the time period between September 2020 and May 2021 out of the 945 patients treated at the Department. Case control matched patients receiving RDV (all in need of supplementary oxygen) and standard of care (SOC) were included as controls. Among the 25 SOT patients (female:male = 11:14; average age = 53.2 ± 12.7 years), 15 received RDV medication (RDV-TX), and in 10 cases SOC treatment was used (SOC-TX). Significantly worse clinical score was noted in RDV patients compared with RDV-TX; however, transfer to a higher intensity care unit as well as 60-day survival of RDV-TX patients were significantly worse. All SOT fatalities within 60 days of follow-up were lung transplant recipients (6 out of 19 lung transplant patients). No adverse events were noted related to RDV therapy. In SOT patients, especially lung transplant recipients, with severe COVID-19 needing supplementary oxygen, RDV treatment was safe; however, outcome was significantly worse as compared with nontransplanted individuals with initially worse clinical parameters., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Interstitial lung disease (ILD) is the leading cause of mortality in systemic sclerosis (SSc). Progressive pulmonary fibrosis (PPF) is defined as progression in 2 domains including clinical, radiological or lung-function parameters. Our aim was to assess predictors of functional decline in SSc-ILD patients and compare disease behavior to that in idiopathic pulmonary fibrosis (IPF) patients. Patients with normal forced vital capacity (FVC > 80% predicted; SSc-ILD: n = 31; IPF: n = 53) were followed for at least 1 year. Predictors of functional decline including clinical symptoms, comorbidities, lung-function values, high-resolution CT pattern, and treatment data were analyzed. SSc-ILD patents were significantly younger (59.8 ± 13.1) and more often women (93 %) than IPF patients. The median yearly FVC decline was similar in both groups (SSc-ILD = −67.5 and IPF = −65.3 mL/year). A total of 11 SSc-ILD patients met the PPF criteria for functional deterioration, presenting an FVC decline of −153.9 mL/year. Cough and pulmonary hypertension were significant prognostic factors for SSc-ILD functional progression. SSc-ILD patients with normal initial spirometry presenting with cough and PH are at higher risk for showing progressive functional decline.

(1) Background: Systemic sclerosis (SSc) is frequently associated with interstitial lung diseases (ILDs). The progressive form of SSc-ILD often limits patient survival. The aim of our study is to evaluate the clinical characteristics and predictors of lung function changes in SSc-ILD patients treated in a real-world setting. (2) Methods: All SSc-ILD cases previously confirmed by rheumatologists and a multidisciplinary ILD team between January 2017 and June 2019 were included ( n = 54). The detailed medical history, clinical parameters and HRCT were analyzed. The longitudinal follow-up for pulmonary symptoms, functional parameters and treatment were performed for at least 2 years in no treatment, immunosuppression and biological treatment subgroups. (3) Results: In SSc-ILD patients (age 58.7 ± 13.3 years, 87.0% women), the main symptoms included dyspnea, cough, crackles and the Raynaud's phenomenon. The functional decline was most prominent in untreated patients, and a normal body mass index (BMI < 25 kg/m 2 ) was associated with a significant risk of deterioration. The majority of patients improved or were stable during follow-up. The progressive fibrosing-ILD criteria were met by 15 patients, the highest proportion being in the untreated subgroup. (4) Conclusions: SSc-ILD patients who are overweight are at a lower risk of the functional decline and progressive phenotype especially affecting untreated patients. The close monitoring of lung involvement and a regular BMI measurement are advised and early treatment interventions are encouraged.

A subset of interstitial lung diseases (ILDs) with autoimmune traits-including connective tissue disease-associated ILD (CTD-ILD) and interstitial pneumonia with autoimmune features (IPAF)-develops progressive fibrosing (PF)-ILD. The aim of our study was to evaluate the clinical characteristics and predictors of longitudinal lung function (LF) changes in autoimmune PF-ILD patients in a real-world setting. All ILD cases with confirmed or suspected autoimmunity discussed by a multidisciplinary team (MDT) between January 2017 and June 2019 ( n = 511) were reviewed, including 63 CTD-ILD and 44 IPAF patients. Detailed medical history, LF test, diffusing capacity of the lung for carbon monoxide (DLCO), 6-min walk test (6MWT), blood gas analysis (BGA), and high-resolution computer tomography (HRCT) were performed. Longitudinal follow-up for functional parameters was at least 2 years. Women were overrepresented (70.1%), and the age of the IPAF group was significantly higher as compared to the CTD-ILD group ( p < 0.001). Dyspnea, crackles, and weight loss were significantly more common in the IPAF group as compared to the CTD-ILD group (84.1% vs. 58.7%, p = 0.006; 72.7% vs. 49.2%, p = 0.017; 29.6% vs. 4.8%, p = 0.001). Forced vital capacity (FVC) yearly decline was more pronounced in IPAF (53.1 ± 0.3 vs. 16.7 ± 0.2 ml; p = 0.294), while the majority of patients (IPAF: 68% and CTD-ILD 82%) did not deteriorate. Factors influencing progression included malignancy as a comorbidity, anti-SS-A antibodies, and post-exercise pulse increase at 6MWT. Antifibrotic therapy was administered significantly more often in IPAF as compared to CTD-ILD patients ( n = 13, 29.5% vs. n = 5, 7.9%; p = 0.007), and importantly, this treatment reduced lung function decline when compared to non-treated patients. Majority of patients improved or were stable regarding lung function, and autoimmune-associated PF-ILD was more common in patients having IPAF. Functional decline predictors were anti-SS-A antibodies and marked post-exercise pulse increase at 6MWT. Antifibrotic treatments reduced progression in progressive fibrosing CTD-ILD and IPAF, emphasizing the need for guidelines including optimal treatment start and combination therapies in this special patient group., Competing Interests: VM, AB, KV, NE received consultation fees from Boehringer Ingelheim during the last 5 years. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nagy, Nagy, Kolonics-Farkas, Eszes, Vincze, Barczi, Tarnoki, Tarnoki, Nagy, Kiss, Maurovich-Horvat, Bohacs and Müller.)

Here we describe the generation of induced pluripotent stem cell lines from each member - male proband, mother, father - of a schizophrenia case-parent trio that participated in an exome sequencing study, and 3 de novo mutations were identified in the proband. Peripheral blood mononuclear cells were obtained from all three individuals and reprogrammed using Sendai virus particles carrying the Yamanaka transgenes. These 3 iPSC lines (iPSC-SZ-HU-MO 1, iPSC-SZ-HU-FA 1, and iPSC-SZ-HU-PROB 1) represent a resource for examining the functional significance of the identified de novo mutations in the molecular pathophysiology of schizophrenia., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Here we describe the generation of induced pluripotent stem cell (iPSC) lines from peripheral blood samples of identical twin sisters with type 2 diabetes mellitus (DM2). Two clonal lines from each patient (HU-DM2-A-1, HU-DM2-A-2 and HU-DM2-B-1, HU-DM2-B-2) were established via Sendai viral reprograming of peripheral blood mononuclear cells, and characterized to confirm pluripotency and genetic integrity. The established iPSC lines can help to investigate DM2 related cellular phenotypes and provide a model system for drug testing., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Taking into account that multidrug resistance (MDR) is the main cause for chemotherapeutic failure in cancer treatment, the ability of novel histamine H 3 receptor ligands to reverse the cancer MDR was evaluated, using the ABCB1 efflux pump inhibition assay in mouse MDR T-lymphoma cells. The most active compounds displayed significant cytotoxic and antiproliferative effects as well as a very potent MDR efflux pump inhibitory action, 3-5-fold stronger than that of reference inhibitor verapamil. Although these compounds possess weak antagonistic properties against histamine H 3 receptors, they are valuable pharmacological tools in the search for novel anticancer molecules. Furthermore, for the most active compounds, an insight into mechanisms of action using either, the luminescent Pgp-Glo™ Assay in vitro or docking studies to human Pgp, was performed., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Pulmonary malignancy is one of the most frequent and fatal cancers in older patients. As data on lower respiratory tract infection (LRTI) and the outcome of lung cancer are scarce, our objective was to determine the impact of LRTI on therapeutic possibilities and one-year mortality., Methods: Patients undergoing bronchoscopy in 2017 who had bronchial microbial sampling at the time of the lung cancer diagnosis (n = 143) were included. Group 1 (LRTI+) included patients with confirmed infection (n = 74) while Group 2 (LRTI-) included patients without infection (n = 69). Clinical characteristics, pathogen profile and one-year survival were analyzed., Results: Age, gender, TNM stage, histology type, comorbidities or underlying lung disease did not differ among groups. The most common LRTI pathogens included aerobic (n = 49), anaerobic (n = 14) and fungal (n = 26) infections. Chemo/immune/target therapy alone, or in combination with radiotherapy were significantly less frequently used, whilst palliative care was more common in Group 1 (LRTI+). Multiple pathogen LRTI patients were significantly older, less frequently diagnosed with adenocarcinoma and had worse performance status compared to solitary pathogen LRTI patients. One-year median survival was 274 days (235 vs. 305 days Group 1 vs. Group 2). Risk factors for increased one-year mortality included performance status ≥2 (OR 30.00, CI 95% 5.23-313.00), performance status 1 (OR 11.87, CI 95% 4.12-33.78), male gender (OR 4.04, CI 2.03-8.04), LRTI with multiple pathogens (OR 2.72, CI 1.01-6.81) and nonadenocarcinoma histology (OR 2.26, CI 1.15-4.56)., Conclusion: LRTIs in lung cancer patients, especially multiple pathogen infections, are associated with less oncotherapeutic possibilities and significant risk for lower one-year median survival., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Connective tissue diseases (CTDs) are all characterized by changes in the adaptive immune system. In the last few decades several CD4 + T lymphocytes and their products have been associated with the development, progression, organ involvement, or therapeutic response of different CTDs. The T helper (Th) T-cell subsets are easy to measure in the peripheral blood, however changes are difficult to interpret. This review summarizes data about Th1/Th2/Th17 and regulatory T-cell (Treg) changes in the most common CTDs. Concordance and divergence of data might help in the better understanding of the common processes of these different systemic autoimmune disorders and might give future clues for differences in disease behavior and treatment response., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: After lung transplantation (LuTX) a high level of immunosuppression is needed to prevent rejection of the graft. Together with earlier colonization by pathogens, immunosuppression makes recipients more susceptible to infections, especially during the first postoperative year. As seasonality of lower respiratory tract infections (LRTI) is well-known in chronic lung diseases, we assessed seasonal changes of pathogen spectrum and number of infections in the first postoperative year in LuTX recipients., Methods: LRTI were analyzed in 28 Hungarian adult LuTX patients. Incidence and spectrum of microorganism causing LRTI were evaluated according to post-transplant time and seasonal temperature and humidity changes., Results: A total of 69 cases of LRTI were registered (average: 1.9 cases/patient; range: 0-14). Gram-negative=59, gram-positive=26, and fungal=31 pathogens were detected, with polymicrobial samples in 46% of all cases. Increased number of LRTI was observed in the cold season (1.68±1.54 vs 0.79±0.92 case/month/patient, P<.01) and significant negative correlations were identified between the incidence of polymicrobial and bacterial infections and temperature (r 2 =0.1535, P<.05, r 2 =0.3144, P<.01, respectively). In addition, positive correlation was observed between polymicrobial infections and humidity (r 2 =0.1403, P<.05). Higher incidence of LRTI was also noted in the cold season, when accounting for the differences in immunosuppression., Conclusion: Seasons influenced the incidence of LRTI in the first postoperative year in LuTX recipients. More intensive vigilance for possible gram-negative and polymicrobial infections is needed in these patients in cold and wet seasons in the continental climate zone, regardless of underlying disease., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Schizophrenia is a severe debilitating psychiatric disorder, with a typical onset in adolescence or early adulthood. This condition is characterized by heterogeneous symptoms (hallucinations, delusions, disorganized behaviour, affective flattening, and social isolation) and a life-time prevalence of 0.5-1.2%. In spite of the efforts to uncover the etiology of the disorder, its pathogenesis and neurobiological background are poorly understood. Given the high heritability in schizophrenia, genetic research remains an important area of focus. Besides the common variations of low penetrance - single nucleotid polymorphisms (SNPs) -, rare variants, mainly copy number variations (CNVs) play a role in the genetic architecture of the disorder. The most frequent CNV associated with schizophrenia is the hemizygous deletion of the 22q11.2 region. According to previous research this genetic variant occurs in 1% of the patients and conversely, 25% of the carriers of the 22q11.2 microdeletion will develop schizophrenia. The 22q11.2 deletion syndrome (22Q11DS, velocardiofacial (VCFS) syndrome, DiGeorge-syndrome) is usually a childhood diagnosis. Its prevalence is 1:2000-4000 considering all births. Patients can demonstrate heart developmental disorders, craniofacial (elongated face, hypertelorism), immunological (thymus-hypoplasia), endocrinological (hypocalcaemia) abnormalities, and neurodevelopmental alterations, but only a proportion will have these abnormalities due to incomplete penetrance. The variable symptoms complicate the recognition of the syndrome in the day to day medical practice. 25% of the known 22Q11DS patients develop schizophrenia but the risk of neuropsychiatric problems, like autism, ADHD and childhood conduct disorder is also increased, while early onset Parkinson's disease in also more frequent in adults. The schizophrenia phenotype is not distinguishable at the moment in patients with or without the 22q11 deletion. But emerging evidence suggests that early onset Parkinson's disease is more frequent in 22Q11DS and the effects of clozapine treatment could be different in schizophrenia with 22Q11DS. The question arises what is the incidence rate of the 22q11.2 microdeletion among our Hungarian DNA samples with schizophrenia. To answer the question, we utilized a new method used in routine genetic diagnostics, multiplex ligation-based probe amplification (MLPA). Although we genotyped the DNA of 315 Hungarian schizophrenia patients, we found no 22Q11DS in this cohort. The findings are discussed in terms of basic research and their translation into everyday clinical practice.

Systemic lupus erythematosus is the most common connective tissue disease that is associated with pulmonary manifestations. Although lupus has the potential to affect any organ, lung involvement is observed during the course of the disease in most cases and it is prognostic for outcome. Pulmonary manifestations in lupus can be classified into five groups based on the anatomical involvement: pleura, lung parenchyma, bronchi and bronchioli, lung vasculature and respiratory muscles can be involved. The most common respiratory manifestations attributable to lupus are pleuritis with or without pleural effusion, pulmonary vascular disease, upper and lower airway dysfunction, parenchymal disease, and diaphragmatic dysfunction (shrinking lung syndrome). In this article the authors summarize lung involvement of lupus, its diagnosis, therapy and prognosis. Orv. Hetil., 2016, 157(29), 1154-1160.

The present work describes a field survey aiming at assessing the impact of a sewage treatment plant (STP) effluent on fish health by means of biomarkers. Indigenous fish were absent downstream of the STP. To elucidate the reason behind this, brown trout (Salmo trutta f. fario) were exposed in floating steel cages up- and downstream of a STP located at the Neckar River near Tübingen (Southern Germany), for 10 and 30 days. A combination of biomarker methods (histopathological investigations, analysis of the stress protein Hsp70, micronucleus test, B-esterase assays) offered the possibility to investigate endocrine, geno-, proteo- and neurotoxic effects in fish organs. Biological results were complemented with chemical analyses on 20 accumulative substances in fish tissue. Even after short-term exposure, biomarkers revealed clear evidence of water contamination at both Neckar River sites; however, physiological responses of caged brown trout were more severe downstream of the STP. According to this, similar bioaccumulation levels (low μg/kg range) of DDE and 12 polycyclic aromatic hydrocarbons (PAHs) were detected at both sampling sites, while up to fourfold higher concentrations of four PAHs, methyl-triclosan and two synthetic musks occurred in the tissues of downstream-exposed fish. The results obtained in this study suggest a constitutive background pollution at both sites investigated at the Neckar River and provided evidence for the additional negative impact of the STP Tübingen on water quality and the health condition of fish.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease involving several organs, including the lungs. Previous results confirmed changes of peripheral T cell subsets in lupus patients; however no data are available about their possible relationship with pulmonary involvement., Objective: To determine pulmonary manifestations and potential relationship in changes of peripheral CD4+ T cell subsets., Methods: Patients with SLE (N = 28) were enrolled in complex pulmonary examination. Patients were divided into groups with pleuropulmonary manifestations (SLEpulm N = 13 age: 44.9 ± 3.3 years, female: male = 11:2) or without (SLEc N = 15 age: 27.2 ± 3.7 years, female: male = 12:3). Peripheral blood was taken for T helper (Th)1, Th2, Th17, CD4+CD25hi+ and regulatory T (Treg: CD4+CD25hi+ CD127-) cell analysis from SLE patients and healthy volunteers (controls, N = 40)., Results: SLEpulm patients were older, had more pulmonary symptoms and significantly decreased pO2 as compared to SLEc group. Ventilatory disorder was present in 92% of SLEpulm patients, with significantly decreased lung volumes, signs of airway involvement and decrease in DLco. Significant increase in Th1/Th2, while decrease in Th17/Treg ratios was present in all SLE compared to controls. In SLEpulm CD4+CD25hi+ subset without changes in Treg number was significantly increased as compared to SLEc and this subgroup of T cell showed significant positive correlation with dynamic lung function parameters and DLco (p < 0.05)., Conclusion: In lupus patients pleuropulmonary manifestations are prevalent and lung function and blood gas measurements should be regularly performed in the daily clinical assessment. Significant increase of activated CD4+CD25hi+ T cells, but not Treg is associated with decreased lung function parameters in SLEpulm patients., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

2,4,7,9-tetramethyl-5-decyne-4,7-diol (TMDD) is a high-production volume chemical used in paper, ink, pesticide, and adhesive industries as a wetting and anti-foaming agent. The physicochemical properties and slow biodegradation rate of TMDD indicate a low bioaccumulation potential but a high prevalence in the environment. As a consequence, TMDD has been detected in several European rivers in the nanogram per liter and lower microgram per liter range; however, its environmental risk to aquatic organisms is considered low. Recent studies almost exclusively focused on acute effects by TMDD, little is known about cytotoxic and genotoxic effects, reproduction and developmental toxicity, endocrine disruption, and any kind of long-term toxicity and carcinogenicity so far. The present study aims to provide more specific baseline information on the ecotoxicological effects of TMDD in fish. For this end, cyto- and genotoxicity assays were carried out in vitro with the permanent fish cell line RTL-W1; in addition, in vivo studies were conducted with the early life stages of zebrafish (Danio rerio) in order to fill the data gaps in developmental toxicity and endocrine disruption. TMDD showed a cytotoxic and slight genotoxic potential in fish cell lines; moreover, various sublethal and lethal effects could be detected in developing zebrafish embryos. There was no evidence of endocrine-disrupting effects by TMDD; however, mortality following prolonged exposure to TMDD during fish sexual development test was clearly higher than mortality in the fish embryo test after 96-h exposure. Our results thus confirmed previous findings of laboratory screening tests, suggesting short-term toxic effects of TMDD in the intermediate, and long-term effects in the lower milligram per liter range.

Objective: Lung cancer carries a relatively high risk of chemotherapy-induced anemia, one of the most frequent hematological complications. Previous data show a lack of optimal anemia correction in patients with chemotherapy-induced anemia. This paper analyzes real-life data considering the prevalence and severity of chemotherapy-induced anemia, together with the frequency and efficacy of erythropoietin treatment of anemia in Hungarian lung cancer patients., Research Design and Methods: Data of 482 patients with histological or cytological confirmed lung cancer receiving chemotherapy were collected retrospectively between 1 January and 31 December, 2008. In all, 83 (17%) of them developed chemotherapy-induced moderate to severe anemia (44.6% male, 55.4% female; mean age 70 ± 8.6 years; NSCLC 67.5%, small cell lung cancer 32.5%)., Results: More than 50% of the patients suffering from moderate to severe chemotherapy-induced anemia (hemoglobin below 10 g/dl) did not receive erythropoietin treatment. Chemotherapy had to be postponed due to anemia in 32.26% of the patients receiving erythropoietin supplementation, while this was seen in 41.94% of the group without erythropoietin treatment (p < 0.05). In patients not receiving erythropoietin, the severity of anemia increased, while erythropoietin treated patients maintained acceptable hemoglobin levels after the end of the chemotherapy., Conclusions: The data draws attention to the fact that nowadays chemotherapy-induced anemia is not treated according to current guidelines in many lung cancer cases in Hungary.

The authors present two cases of atraumatic (spontaneous) thoracic lung hernias, which are extreme rarities in the international literature, too. Risk factors and clinical pictures discussed and operative treatments are demonstrated. The spontaneous thoracic (intercostal) hernias were provoked by intractable cough caused by chronic obstructive pulmonary disease (COPD) in both cases. Multi-slice spiral CT (MSCT) scan as well as the secondary 3D 'volume rendering' (VRT) reconstructions unequivocally suggested this rare condition. Provided with the exact diagnosis, the surgical correction of the thoracic wall resulted in full recovery of the two patients. Finally, the authors briefly discuss data of thoracic hernias published in the Hungarian and the international literature. They conclude that the awareness of this extremely rare condition is important due to the high prevalence of COPD as a risk factor. Diagnostic imaging demonstrated can provide significant help in the correct diagnosis of similar cases.

Thoracoscopic sympathectomy (VATS) is routinely used to treat severe palmar and axillary hyperhydrosis. The authors present a novel method: one-stage bilateral VATS-sympathectomy. Special considerations also discussed regarding the anaesthesia and operative technique of the procedure. The history of surgical therapy of hyperhidrosis is reviewed briefly, too. The authors conclude that one-stage bilateral VATS-sympathectomy for palmar and axillary severe hyperhidrosis is a safe and effective method, patient satisfaction improves and cost is significantly decreased due to shorter hospital stay.

The authors summarize their therapeutic methods of palmar and axillary hyperhidrosis in this article. They discuss the characteristics, frequency of upper limb and patho-anatomical features of chronic sweating. Authors summarized their almost 40 years experience in treatment methods, technological improvements as well as they review recent knowledge and relevant literature. The open thoracotomic desympathization applied in the beginnings was gradually replaced by a minimally invasive VATS-sympathectomy (Video Assisted Thoracoscopic Surgery). The possibilities of conservative treatments, local excision methods will also be discussed, as well as the application and efficiency of Botox-treatments that are used in plastic surgery. The mean frequency of 0.1-1.0% described in scientific literature is indicative of a significant number of unresolved cases, which thus requires more efficient diagnostic and patient orientation practices. Based on their experiences, the most efficient treatment of upper limb hyperhidrosis is the thoracic sympathectomy (ramicotomy and the relevant T(2) -T(3) ganglia) according to Smithwick-procedure and modified by others. If necessary, one-stage bilateral VATS-surgery may be applied. Another effective conservative possibility is the Botox-therapy, which they had applied individually at the plastic surgery clinic. Significant complications or compensatory hyperhidrosis were not detected.

A case of spontaneous thoracic (intercostal) lung herniation originating from a chronic obstructive pulmonary syndrome (COPD) is presented. The authors present the classification, the clinical aspects and the patho-anatomic features of hernia along with the steps of diagnostic procedures. They discuss the potential pathomechanism of intercostal muscle disruption and the attached literature of this disease. The thoracic wall herniation was detected via a chest radiograph and confirmed by CT-imaging with the help of a special "3D" reconstruction-method. The knowledge of rare lung herniation is important because of the huge increase in the number of COPD-cases in our country recently.

Unlabelled: INTRODUCTION, OBJECTIVES: Authors of two thoracic surgical departments from the above named hospitals discuss their practices of pulmonary metastasectomy after pneumonectomy for malignant disease., Material and Methods: Six patients were operated after pneumonectomy for metastatic spread in the residual lung. The average age of the three male and three female patients was 52.5 years. The applied preoperative diagnostical methods were the following: chest-x-ray, CT scan, MRI, PET-CT scan, perfusion lung scintigraphy, bronchological examinations, functional respiratory tests, ECG, cardiac echo, arterial blood gases (ABGs) and other laboratory analyses. Patient selection for operation was based on strict oncological and cardiorespiratory criteria. Finally, the authors describe the applied operative technique; atypical mechanical resection with stapler., Results: Mean length of postoperative intensive care was between 3 to 7 days, while that of hospitalization altogether was 13 to 18 days (average 15.2 days). Ventilation needed for one patient for 5 days approximately. Two of the six patients' survival was 18 and 25 months after pulmonary metastasectomy. Four patients are still alive, their average postoperative survival is 33.5 months. They are followed up regularly and their quality of life is satisfactory., Conclusions: The key factors that determine the successful outcome of metastasectomies are careful and personalized evaluation of the patients, their condition and fitness for thoracotomy, stabile cardiopulmonary functions and the capacity of the residual lung. Multidisciplinary teamwork involving anaesthetists and intensive care specialists along with surgeons using the quick atypical resection technique are the key elements to improved survival of these patients.

More than thousand plastic operations were performed in our departments with ROMICRO-set during the last ten years. First we applied it for reconstructive and aesthetic augmentation of the breast. Thereafter, we developed new technique for gynecomastia and reconstruction of diastasis of the m. rectus abdominis sheath. According to our experience, the ROMICRO-set is a useful tool in plastic surgery. The ROMICRO-set can be used through a small incision to achieve three dimensional views with excellent exposure and lighting.

We describe the results of an operative method applied in patients suffering from refractory ascites. Instead of the well-known shunt-implants we started to re-use Ruotte's method, which was published 100 years ago. According to our observations the anastomosis formed by the long saphenous vein and the peritoneal surface eliminates not only the known complications of the traditional shunt-operations but also provides an effective early and a late ascites inflow. The flow of the ascites was convincingly proven by regularly performed colour Doppler UH tests. This old/new method is applicable in patients with therapy-resistant ascites to eliminate the traditional shunt-models.

Transposition of the gallbladder to the left side without situs inversus viscerum is rare. These gallbladders are almost always situated under the left lobe of the liver between the IV and III segments or on the III segment to the left of the falciform ligament. One left positioned gallbladder was found in a consecutive series of 2536 patients undergoing microlaparotomy cholecystectomy for symptomatic gallstone disease in the "Moritz Kaposi" Teaching Hospital between 1990 and 2000, a prevalence of 0.04 per cent. Despite of the abnormal position of the gallbladder, the biliary pain experienced by the patient was on the right side. Preoperative diagnosis of this anomaly was not made in this patient despite preoperative sonography. The cystic duct may open in the common hepatic duct either side. In this anomaly safe microlaparotomy cholecystectomy or laparoscopic cholecystectomy can be performed.

The authors present their experiences in treatment of chronic pancreatic abscess and infected pancreatic necrosis. In this paper they refer to patients only whose acute necrotizing pancreatitis occurred 4-6 weeks earlier and had intra- and peripancreatic abscesses. They describe their successful lavage method for treatment of pancreatic abscesses. Between 1985 and 1998 they treated 16 patients with only one mortality. The majority of their patients were relatively old and most of them suffered from several severe unrelated diseases. In their opinion, careful dissection and long period of lavage and drainage are a successful method for treating this high-risk surgical group.

Authors explains his operational procedure for the treatment of refractory ascites to replace generally used shunt types (LeVeen, Denver, Agishi). It means leading ascites fluid from the abdominal cavity into the venous system with the help of a silicone drain. For maintaining one-way flow they he used the double saphenous valve before the sapheno-femoral junction. They gives a step by step description of the procedures applied during the operation and also explains the first results. The method well deserves attention and further examination because it is simple, cheap and reliable due to the use of saphenous valves coming from the body itself.

Authors summarize their experiences connected with the treatment of open wounds of the heart and the pericardium during the past 35 years. Between 1962 and 1997 the authors operated on 31 cases of injuries affecting the heart. 10 wounds were situated in the isolated pericardium. They also deal with the history of treating injuries of the heart and pericardium. The value of diagnostical procedures was analysed and compared with Hungarian literature data that describes further cases. They emphasize the importance of immediate physical examination (including that of circulation, breathing, heart rate, consciousness, etc.) in cases of wounds close to the heart. Authors discuss the effects and the importance of the circumstances that directly affect the life expectancy of the patient during the treatment, such as time factor, the planning of cooperation within the operating team, practice in the field of thoracic surgery and management. They also put stress on correct thoracotomy, drainage and suction, so as to avoid postoperative pleural complications.

Microlaparotomy cholecystectomy (MLC) is an alternative for minimal invasive surgical interventions of the biliary tract. In Hungary over 7000 operations were performed in 21 surgical departments as at December 31. 1998 and numerous additional departments have indicated their demand for the initiation of the method. Every new surgical procedure requires a "learning curve" during the application of MLC, difficulties encountered with the surgical solution occurred in a 14-15% range. We studied difficulties noticed during micro-, minilaparotomy cholecystectomy in 2400 unselected cases from the adoption of the surgical method in our department until December 31, 1998. We grouped our findings into avoidable, and unavoidable difficulties. Circumstances that can present unavoidable difficulties include: the patient's abnormal change in build, surgical interventions that have to be performed on patients 8-10 days after obstructive cholecystitis, abnormal gallbladder not indicated during preoperative examination, as well as biliary tract variations. A considerable part of the difficulties can be avoided by MLC-desirable positioning of the patient on the operating table, appropriate choice of surgical incision site and method, satisfactory anaesthesia, the use of necessary instruments suitable for exposure and unobjectionable illumination of the surgical area, as well as the performance of cholecystectomy with required modifications per given circumstances. The concomitant 2.5-16% alternating conversion rate after minicholecystectomy is indicative of the importance of the use of instruments assuring adequate exposure and excellent illumination of the surgical area. During the practice in our department this occurrence was recorded in 0.29% with the use of the ROMICRO R-set.

The authors introduce a case of a 41 years old male patient who was examined first on pulmonology department due to thoracic pain, haemoptoe and fever. In the background of symptoms a 10 cms diameter formation was found in the right thorax side joined to the hilus. Even a through row of examination was unable to determine the histologic type. After the patient's admittance to the authors' thoracic surgery department the tumor occupying the central part of the right upper pulmonary lobe was resected by lobectomy via right thoracotomy. The histologic result was monophasic synovial sarcoma of which primary pulmonary appearance is very rare. The authors consider the rarity of this tumor type worth to publish.

The authors introduce their experiences on intracavital chemotherapy of mainly secondary pleural and pericardial malignant effusions based on a 5 years term of routinely used practise. In the cases of patients proper to the indicational conditions palliative regional cytostatic treatment was applied through transthoracal and intraopericardial (inserted by modified Fontenelle method) drains in order to cessate definitively the exsudation to improve the quality of life.

The authors summarize their experiences on the surgical treatment of pericardial effusions by surveying the clinical data of patients in the last 4 years. They call attention on the advantages of subxyphoideal pericardium fenestration, the modified Fontenelle operation, which method is routinely used by them.