Evidence for oxidative stress in bronchiolitis obliterans syndrome after lung and heart-lung transplantation. The Munich Lung Transplant Group

Bronchiolitis obliterans syndrome (BOS) is the most serious long-term sequel of lung or heart-lung transplantation (H/LTX). Neutrophilia in the lower respiratory tract is a prominent feature of BOS. Because polymorphonuclear leukocytes (PMN) are capable of releasing large quantities of reactive oxygen species, we measured indicators of oxidative stress and glutathione levels representing antioxidant defense in H/LTX patients (HLTX, n=6; double-LTX, n=7; single-LTX, n=9). We analyzed 19 bronchoalveolar lavage (BAL) samples from 13 non-BOS patients (nine female, four male: age 39+/-4 years) and 17 BAL samples from nine BOS patients (five female, four male: age 33+/-2 years). PMN were the predominant BAL cell population in BOS (61.7+/-7.8% vs. 12.3+/-3.4%, P<0.001). Myeloperoxidase activity in the epithelial lining fluid and oxidized methionine residues in BAL-derived proteins were elevated in BOS (8.6+/-1.6 U/ml vs. 2.2+/-0.6 U/ml, P<0.01; and 12.6+/-1.1% vs. 7.7+/-0.8%, P<0.001, respectively). In addition, the concentration of reduced glutathione in epithelial lining fluid was decreased in BOS (162.6+/-20.1 microM vs. 345.8+/-57.1 microM, P<0.01), whereas the proportion of oxidized glutathione was increased (13.9+/-2.0O% vs. 6.7+/-1.2%, P<0.001). PMN, myeloperoxidase, and oxidized methionine residues were inversely correlated, whereas reduced glutathione was positively correlated with forced expiratory volume in 1 sec (P<0.05 to P<0.001). We conclude that excessive oxidative stress and a lack of glutathione are associated with BOS after H/LTX and may play relevant roles in the development of this disorder.     

Berufskrebs Stellenwert von Biomarkern in der Risikofaktorenanalyse von Karzinomen der Kopf-Hals-Region

Am 17.10.1997 fand der zweite Workshop der Arbeitsgruppe Berufskrebs innerhalb der Arbeitsgemeinschaft Onkologie der Deutschen Gesellschaft für Hals-Nasen-Ohrenheilkunde, Kopf- und Halschirurgie, in Heidelberg statt. Die abgehandelten Schwerpunktthemen werden nachfolgend kurz dargestellt.     

Neuropathological abnormalities of the corpus callosum in schizophrenia: a diffusion tensor imaging study

OBJECTIVES: Diffusion tensor imaging (DTI), a technique capable of examining water diffusion in different tissues and the organisation of white matter tracts, was used to investigate the neuropathology of the corpus callosum in vivo in patients with schizophrenia. METHODS: Diffusion tensor imaging was performed in 20 schizophrenic patients and 25 healthy controls. Two complementary measures, mean diffusivity and fractional anisotropy, which are considered to be sensitive indices of axonal integrity, were obtained from regions of interest in the genu (anterior) and splenium (posterior) of the corpus callosum. RESULTS: Mean diffusivity was significantly increased and fractional anisotropy significantly reduced in the splenium but not the genu of the corpus callosum in the schizophrenic group compared with controls. There were no significant sex differences in the DTI measures for either the schizophrenic or control group. Clinical variables such as age, duration of illness, dose of antipsychotic medication, and schizophrenic symptoms did not predict the DTI changes in the schizophrenic patients. CONCLUSIONS: The presence of DTI changes in the splenium but not the genu of the corpus callosum suggests that there may be a focal disruption of commisural connectivity in schizophrenia. However, these findings do not exclude the possibility of abnormalities in other areas of the corpus callosum or other regions of white matter and further research using different methods of analysis may enable us to clarify this. Diffusion tensor imaging is a valuable tool in investigating the structure of white matter in schizophrenia.     

Staging of rectal cancer by double-contrast MR imaging using the rectally administered superparamagnetic iron oxide contrast agent ferristene and IV gadodiamide injection: results of a multicenter phase II trial

The aim of this study was to assess the accuracy of double-contrast magnetic resonance imaging (MRI) with rectal application of the superparamagnetic iron oxide contrast agent (SPIO) ferristene and IV gadodiamide for preoperative staging of rectal cancer. In a randomized phase II dose-ranging trial, 113 patients were studied preoperatively with one of four different formulations of ferristene (Abdoscan) as an enema before MRI. T1-weighted spin-echo (T1w SE) and T2w turbo spin-echo (TSE) single-contrast images were obtained as well as T1w SE and gradient-echo (GRE) double-contrast images after IV gadodiamide injection (Omniscan). Images were assessed qualitatively, and TNM tumor stage was compared with histopathology. High-viscosity ferristene formulations were superior to low-viscosity formulations in tumor staging (accuracy 90% vs 74%, P < 0.01). There was no significant difference between high and low iron content ferristene. MRI had a sensitivity of 97%, specificity of 50%, and accuracy of 82% for staging of rectal carcinoma higher than T2 stage. At receiver operator characteristic (ROC) analysis, MR differentiation between T1/T2 and T3/T4 tumor stages yielded a ROC index of 0.848. Double-contrast MRI is an accurate method for preoperative staging of rectal cancer.     

The epidemiology of fractures of the distal femur

Between 1980 and 1989, reports on 2,165 fractures of the distal part of the femur (1,051 women and 1,114 men) were collected by AO Documentation and are analyzed in the present paper. The number of fractures showed a bimodal pattern with a marked variation in the number of fractures in relation to gender and age. A larger prevalence of fractures was observed either in young men (about 20 years old, traffic or sport) and in old women (about 70, fall at home, osteoporosis).     

A quality assessment tool to evaluate tocolytic studies

Over the past 15 years, the use of β-agonists has declined worldwide. Following the Royal College of Obstetricians and Gynaecologists guidelines in 2002, clinicians in the UK and beyond were faced with the dilemma of continuing to use β-agonists, desist from using tocolytic therapy completely or choosing to change to atosiban or calcium channel blockers (CCBs). While grade A level 1 evidence exists to show that atosiban is significantly more efficacious than placebo and significantly safer than β-agonists for the treatment of spontaneous preterm labour, the evidence for CCBs, such as nifedipine, is much less robust and no placebo-controlled trials have been performed. Published studies on nifedipine are largely investigator-led studies of small sample size, which lack sufficient power. As a result, most of the evidence has been based on meta-analyses of these studies, which look retrospectively at pooled data and are only as good as the quality of the studies included. In light of this, a tool was developed to produce a systematic review of studies on tocolytic effectiveness, which can and should be applied to all tocolytics and which considered both method- and topic-specific markers of quality. In the process of applying this tool to nifedipine, an extensive literature search identified 31 studies for a systematic review of the quality of nifedipine studies assessed by eight paired reviewers with wide experience in the subject of spontaneous preterm labour and preterm birth. Forty topic- and method-specific items of quality were assessed. The paucity of good quality studies of nifedipine used for the treatment of spontaneous preterm labour should be highlighted in meta-analyses or systematic reviews, which measure efficacy and should limit and influence the degree to which recommendations and guidelines are made on the basis of such studies.     

Cognitive improvement in schizophrenic patients does not require a serotonergic mechanism: randomized controlled trial of olanzapine vs amisulpride.

Combined serotonin-2A (5-HT(2A)) and dopamine-2 (D2) receptor blockade has been proposed as a candidate mechanism by which second-generation antipsychotics (SGAs) improve both cognition and negative symptoms in schizophrenic patients, in contrast to antipsychotics of the first generation. The SGA amisulpride, however, only binds to D2/D3 receptors, which makes it an interesting tool to test this assumption. In a randomized controlled trial, 52 schizophrenic patients were allocated to treatment with either olanzapine (10-20 mg/day) or amisulpride (400-800 mg/day). A comprehensive neuropsychological test battery and clinical ratings were used to assess participants at inclusion and after 4 and 8 weeks. Cognitive improvements of moderate size were observed, with effect sizes similar to those obtained in previous studies on the cognitive effects of SGAs. Importantly, amisulpride was not inferior to olanzapine for any cognitive domain. Combined 5-HT(2A)/D2 receptor blockade is probably not necessary for cognitive improvement by SGAs.     

Seroconversion rate and socio-economic and ethnic risk factors for SARS-CoV-2 infection in children in a population-based cohort,Germany, June 2020 to February 2021

IntroductionSocio-economic and ethnic background have been discussed as possible risk factors for SARS-CoV-2 infections in children. Improved knowledge could lead to tailored prevention strategies and help improve infection control.AimWe aimed to identify risk factors for SARS-CoV-2 infections in children in the first and second wave of the pandemic.MethodsWe performed an observational population-based cohort study in children (6 months–18 years) scheduled for legally required preventive examination and their parents in a metropolitan region in Germany. Primary endpoint was the SARS-CoV-2 seroconversion rate during the study period. Risk factors assessed included age, pre-existing medical conditions, socio-economic factors and ethnicity.ResultsWe included 2,124 children and their parents. Seroconversion rates among children in all age groups increased 3–4-fold from June 2020 to February 2021. Only 24 of 58 (41%) seropositive children reported symptoms. In 51% of infected children, at least one parent was also SARS-CoV-2-positive. Low level of parental education (OR = 3.13; 95% CI: 0.72–13.69) non-significantly increased the risk of infection. Of the total cohort, 38.5% had a migration background, 9% of Turkish and 5% of Middle Eastern origin, and had the highest risk for SARS-CoV-2 infections (OR = 6.24; 95% CI: 1.38–28.12 and OR = 6.44 (95% CI: 1.14–36.45) after adjustment for other risk factors.ConclusionIn the second half of 2020, seroprevalence for SARS-CoV-2 in children increased especially in families with lower-socioeconomic status. Culture-sensitive approaches are essential to limit transmission and could serve as a blueprint for vaccination strategies.