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Christina Hoffmann,1 Marc Hanisch,1 Jana B Heinsohn,1 Vanessa Dostal,1 Melissa Jehn,1 Uta Liebers,1 Wulf Pankow,2 Gavin C Donaldson,3 Christian Witt1 1Division of Ambulatory Pneumology, Charité – Universitätsmedizin Berlin, Berlin, Germany; 2Division of Pneumology and Infectiology – Thoracic Center, Vivantes Klinikum Neukölln, Berlin, Germany; 3Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK Purpose: Patients with COPD show an increase in acute exacerbations (AECOPD) during the cold season as well as during heat waves in the summer months. Due to global climate changes, extreme weather conditions are likely to occur more frequently in the future. The goal of this study was to identify patient groups most at risk of exacerbations during the four seasons of the year and to determine at which temperature threshold the daily hospital admissions due to AECOPD increase during the summer.Patients and methods: We analyzed retrospective demographic and medical data of 990 patients, who were hospitalized for AECOPD in Berlin, Germany. The cases were grouped into the following cohorts: “spring” (admission between March and May), “summer” (June – August), “autumn” (September – November), and “winter” (December – February). AECOPD hospital admissions from 2006 and 2010 were grouped into a “hot summer” cohort and cases from 2011 and 2012 into a “cold summer” data-set. Climate data were obtained from the German Meteorological Office.Results: Patients hospitalized for a COPD exacerbation during winter were significantly older than summertime patients (P=0.040) and also thinner than patients exacerbating in spring (P=0.042). COPD exacerbations during hot summer periods happened more often to patients with a history of myocardial infarction (P=0.014) or active smokers (P=0.011). An AECOPD during colder summers occurred in patients with a higher Charlson index, who suffered in increased numbers from peripheral vascular diseases (P=0.016) or tumors (P=0.004). Summertime hospital admissions increased above a daily minimum temperature of 18.3°C (P=0.006).Conclusion: The identification of COPD patient groups most at risk for climate related exacerbations enables climate-adapted prevention through patient guidance and treatment. In view of global climate changes, discovering vulnerabilities and implementing adaptive measures will be of growing importance. Keywords: COPD, acute exacerbation, seasonal phenotype, urban heat island, heat stress, climate change

To determine the most relevant pathogens for CAP in Germany, patients with radiologically confirmed pulmonary infiltrates and at least one clinical sign of lung infection were prospectively recruited within the CAPNETZ cohort from 2004 until 2016. In 990 out of 4.672 patients (21%) receiving complete diagnostics the most prominent change of pathogens was a decrease of S. pneumoniae (58% in 2004 to 37.5% in 2016; p ≤ 0.001, ρ = − 0.148) and an increase of H. influenzae (12.2% to 20.8%; p = 0.001, ρ = 0.104). [ABSTRACT FROM AUTHOR]

O bjectives To investigate possible interactions visible on electroencephalogram recordings caused by concomitant administration of marbofloxacin and carprofen or cimicoxib in dogs without central nervous system disease. M ethods Totally 21 client-owned dogs undergoing different surgeries were included in a randomised, blinded, clinical study. Each dog was assigned to one of two groups treated with either carprofen or cimicoxib pre- and postoperatively. After anaesthetic induction both groups received marbofloxacin intravenously while recording an electroencephalogram. Offline electroencephalogram analysis included qualitative evaluation and Fast Fourier Transformation. Postoperative analgesia was evaluated for 24 hours and after 10 days with the short-form Glasgow Composite Measure Pain Scale. Statistical analysis included Wilcoxon signed rank test, Mann-Whitney U test and Student's t-test with α set at 5%. R esults Marbofloxacin injection caused no effects on quantitative and qualitative electroencephalogram parameters in both groups. No differences in postoperative pain scoring were found between treatment groups. C linical S ignificance Concurrent use of marbofloxacin with either cimicoxib or carprofen did not induce neuroexcitatory activities in dogs without CNS disease directly after administration. [ABSTRACT FROM AUTHOR]

Mycorrhizas of six spruces of a stand were collected over two years and were analysed for soluble carbohydrates (sucrose, raffinose, glucose, trehalose and mannitol). The level of these carbohydrates was high during winter and low during summer. Upon exposure of excised mycorrhizas to frost or desiccation, the content of trehalose roughly doubled. A positive correlation was found between the trehalose content of mycorrhizas and their ability to survive frost or desiccation as determined by the electrolyte leaching method. [ABSTRACT FROM AUTHOR]

Abstract Background Interferon-gamma release assays (IGRA) are used for tuberculosis (TB) screening in healthcare workers (HCWs). However, data on specificity of IGRA in serial testing of HCWs is sparse. Therefore the specificity and the negative predictive value of the IGRA - QuantiFERON-TB Gold In-Tube (QFT) - in German nursing students was investigated. Methods 194 nursing students at the start of their professional career were tested with the QFT. 14 nursing students were excluded from the specificity analysis, due to exposure to mycobacterium tuberculosis. Two of these subjects were QFT- positive. None of them developed disease during the year of follow-up. A study group of 180 students, all with very low risk of prior TB infection, remained in the specificity analysis. Subjects were monitored for at least two years with respect to the development of active TB disease. IGRA was performed at the start of the training and after one year. Results The mean age of the study group (n = 180) was 23 years (range 18-53) with 70.9% female and 99.4% German born. The specificity of QFT was 98.9% (178/180; 95% CI 0.96-0.99); lowering the cut-off from 0.35 IU/ml to 0.1 IU/ml would have decreased specificity only slightly to 97.8% (176/180; 95% CI 0.94-0.99). Of the 154 nursing students available for re-testing, one student who initially scored positive reverted to negative, and one student initially negative converted to positive. None of the monitored group with initially negative QFT results developed TB disease, indicating a high negative predictive value of the IGRA in this population. Conclusions Following our data, QFT can serve as an effective tool in pre-employment TB screenings for HCWs. As its negative results were stable over time, specificity of the QFT in serial testing of HCWs is high. As the risk of acquiring TB infection in the German healthcare system appears to be low, our data supports the recommendation of performing TB screening only in those HCWs with known contact to TB patients or infectious materials.

Background: Smoking cessation is one of the most powerful health promotion tools in the Western world. Behavioral group therapies are regarded as very promising interventions in this field. Quitting rates are usually evaluated after 6-12 months and lie between 30 and 45%. So far, there are no scientific data on potential protective indicators to remain successfully smoke free after this period. Therefore, the aim of this study was to detect the current smoking status of former participants of a cessation service in an urban German surrounding. We investigated reasons for relapses, quitting strategies, and psychosocial parameters., Methods: In 2019, 130 former patients (2011-2017; mean age 54 years; 37 pack/years; Fagerstroem = 5.75; 58.5% male, 41.5% female; 66% physical comorbidities; 35% psychiatric diagnoses) were invited to participate in a mailed survey (including WHO 5, SF 12, self-efficacy scale) and were asked about their current smoking status, personal history of smoking, and individual experiences with stopping after the 1‑year abstinence date., Results: A total of 53 persons replied (RR 41%), 29 (54%) of whom are currently smoke free; 24 relapsed intermittently or permanently, 9 experimented with e‑cigarettes, and 2 became dual users. Daily hassles as well as physical and mental challenges were the main reasons for relapsing., Conclusion: Due to the low response rate, conclusions are limited; however, the 1‑year abstinence rate might not be as reliable as thought so far; long-term "sober" nicotine addicts remain at risk of relapse., (© 2021. Springer-Verlag GmbH Austria, ein Teil von Springer Nature.)

Introduction: Sources of infection of most cases of community-acquired Legionnaires' disease (CALD) are unknown., Objective: Identification of sources of infection of CALD., Setting: Berlin; December 2016-May 2019., Participants: Adult cases of CALD reported to district health authorities and consenting to the study; age and hospital matched controls., Main Outcome Measure: Percentage of cases of CALD with attributed source of infection., Methods: Analysis of secondary patient samples for monoclonal antibody (MAb) type (and sequence type); questionnaire-based interviews, analysis of standard household water samples for Legionella concentration followed by MAb (and sequence) typing of Legionella pneumophila serogroup 1 (Lp1) isolates; among cases taking of additional water samples to identify the infectious source as appropriate; recruitment of control persons for comparison of exposure history and Legionella in standard household water samples. For each case an appraisal matrix was filled in to attribute any of three source types (external (non-residence) source, residential non-drinking water (RnDW) source (not directly from drinking water outlet), residential drinking water (RDW) as source) using three evidence types (microbiological results, cluster evidence, analytical-comparative evidence (using added information from controls))., Results: Inclusion of 111 study cases and 202 controls. Median age of cases was 67 years (range 25-93 years), 74 (67%) were male. Among 65 patients with urine typable for MAb type we found a MAb 3/1-positive strain in all of them. Compared to controls being a case was not associated with a higher Legionella concentration in standard household water samples, however, the presence of a MAb 3/1-positive strain was significantly associated (odds ratio (OR) = 4.9, 95% confidence interval (CI) 1.7 to 11). Thus, a source was attributed by microbiological evidence if it contained a MAb 3/1-positive strain. A source was attributed by cluster evidence if at least two cases were exposed to the same source. Statistically significant general source types were attributed by calculating the population attributable risk (analytical-comparative evidence). We identified an external source in 16 (14%) cases, and RDW as source in 28 (25%). Wearing inadequately disinfected dentures was the only RnDW source significantly associated with cases (OR = 3.2, 95% CI 1.3 to 7.8) and led to an additional 8% of cases with source attribution, for a total of 48% of cases attributed., Conclusion: Using the appraisal matrix we attributed almost half of all cases of CALD to an infectious source, predominantly RDW. Risk for LD seems to be conferred primarily by the type of Legionella rather than the amount. Dentures as a new infectious source needs further, in particular, integrated microbiological, molecular and epidemiological confirmation., Competing Interests: The authors have declared that no competing interests exist.

Background: Estimates of the prevalence of chronic obstructive pulmonary disease (COPD) in Germany range from 1.9% to 13.2%, depending on the population studied and the investigative methods used. About 30% of all patients already have severe airway obstruction by the time the condition is diagnosed., Methods: Review of pertinent literature retrieved by a selective search, including current guidelines and textbooks., Results: Smoking is the main risk factor for COPD. The diagnosis is based on characteristic symptoms that patients at risk should be actively asked about-cough, dyspnea, diminished physical reserve, and frequent airway infections-together with abnormal pulmonary function tests. Spirometry usually suffices to document impaired air flow. The clinical evaluation and the treatment strategy are based on the severity of airway obstruction and dyspnea, and the frequency of exacerbations. According to a European study, dyspnea is present in 73% of persons with severe COPD, expectoration in 64%, cough in 59%, and wheezing in 42%. Asthma, congestive heart failure, and interstitial lung disease are the main differential diagnoses., Conclusion: COPD may begin with symptoms that are only mild at first even in a longstanding smoker. The available diagnostic techniques need better prospective validation with respect to relevant endpoints, including mortality, symptom progression, quality of life, and frequency of exacerbations.

Background: Healthcare workers (HCW) are a risk group for tuberculosis (TB). That is why interferon-gamma release assay (IGRA) serial testing is performed on HCWs repeatedly exposed to infectious patients or materials. However, the variability of IGRA in serial testing is not yet well understood. We therefore analysed the prevalence of positive IGRA results as well as conversion and reversion rates in the serial testing of healthcare trainees in a low-incidence country., Methods: In a prospective cohort study, all trainees (n=194) who began training as a nurse or healthcare worker at the Vivantes Healthcare Training Institute in Berlin on 1 October 2008 or 1 April 2009 were IGRA-tested at three different times during the three years of training. Socio-demographic data and possible risk factors (e.g., TB contacts, time spent abroad, area of work) were recorded by means of a standardised questionnaire. The QuantiFERON Gold In-Tube (QFT) was used as an IGRA., Results: At the beginning of the training the cohort comprised 194 trainees. 70% were female. Their average age was 23. The prevalence of positive QFT was 2.1% (4/194). In the first follow-up test, 2 out of 154 (1.3%) tested IGRA-positive, 151 (98%) had constantly negative results. One IGRA was constantly positive (0.6%) and there was one conversion and one reversion (0.6% respectively). In the second follow-up (n=142) there was again one conversion (0.7%), one reversion and the one constantly positive test result in all three QFT. This trainee had active TB in 2002. All other test results were constantly negative (n=139; 98%). No case of active tuberculosis was diagnosed over the three-year observation period. Contact with TB patients was reported by 42 (29.6%) trainees during the follow-up. The two trainees with a conversion in QFT had no known contact with TB patients. Discordant results in the three consecutive QFT were observed in three trainees (2.1%). Using a borderline zone from 0.2-0.7 IU/mL reduced the number of trainees with discordant results from three to one - a reversion., Conclusion: The prevalence rate of latent TB infection is low in healthcare trainees without known risk factors for TB infection in their history. The infection risk seems to be low in this population even though contacts with TB patients during the training were reported. Introducing a borderline zone for the interpretation of reversions and conversions in this cohort appears to be safe and reduces the number of discordant results and helps to avoid unnecessary chest X-rays and preventive treatment.

Tobacco consumption is a major public health threat. Healthcare workers can contribute to the reduction of tobacco use. The principles of intervention need to be provided already during vocational school. This research examines the smoking habits, the personal attitudes towards smoking and the professional beliefs of healthcare trainees. The aim of this study is to ascertain the necessity and the general conditions for multilevel interventions of prevention and health promotion. In 2010, a questionnaire survey was conducted in a Berlin vocational school for healthcare workers. Of 148 students (RR = 49.3%) 41.9% of the students are daily or occasional smokers. The nicotine dependency and the number of cigarettes per day are comparatively low. The majority of smoking students is willing to quit and has already undertaken several attempts. Non-smoking protection is evaluated to be very important and intervention rates in patient care range between 49% and 72%. In both questions, non-smokers and smokers differ significantly. The self-reported smoking prevalence in our population is considerably lower than in previous studies. However, the smoking rate among healthcare trainees is still higher than in the general population. The students' own smoking behaviours and its influences on the treatment of patients should be reflected during school. It is necessary to develop adequate recruitment strategies and attractive interventions for this target group., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Interferon-gamma release assays (IGRA) are used for tuberculosis (TB) screening in healthcare workers (HCWs). However, data on specificity of IGRA in serial testing of HCWs is sparse. Therefore the specificity and the negative predictive value of the IGRA - QuantiFERON-TB Gold In-Tube (QFT) - in German nursing students was investigated., Methods: 194 nursing students at the start of their professional career were tested with the QFT. 14 nursing students were excluded from the specificity analysis, due to exposure to mycobacterium tuberculosis. Two of these subjects were QFT- positive. None of them developed disease during the year of follow-up. A study group of 180 students, all with very low risk of prior TB infection, remained in the specificity analysis. Subjects were monitored for at least two years with respect to the development of active TB disease. IGRA was performed at the start of the training and after one year., Results: The mean age of the study group (n = 180) was 23 years (range 18-53) with 70.9% female and 99.4% German born. The specificity of QFT was 98.9% (178/180; 95% CI 0.96-0.99); lowering the cut-off from 0.35 IU/ml to 0.1 IU/ml would have decreased specificity only slightly to 97.8% (176/180; 95% CI 0.94-0.99). Of the 154 nursing students available for re-testing, one student who initially scored positive reverted to negative, and one student initially negative converted to positive. None of the monitored group with initially negative QFT results developed TB disease, indicating a high negative predictive value of the IGRA in this population., Conclusions: Following our data, QFT can serve as an effective tool in pre-employment TB screenings for HCWs. As its negative results were stable over time, specificity of the QFT in serial testing of HCWs is high. As the risk of acquiring TB infection in the German healthcare system appears to be low, our data supports the recommendation of performing TB screening only in those HCWs with known contact to TB patients or infectious materials.

In six awake healthy adults we studied the physiological effects of mechanical unloading of the respiratory muscles during increased ventilatory demand. We were interested in whether respiratory muscle activity is down regulated and if this is mainly a consequence of chemical factors, i.e. CO2-reduction, or non-chemical neuromuscular inhibition. With 33 mmHg inspiratory CO2 we induced modest hyperpnea of 24.4 +/- 3.9 L/min. Proportional assist ventilation (PAV) was applied with flow-related assist of 2.5 cm H2O/L/s and volume-related assist of 6 cm H2O/L. Respiratory muscle activity was measured by transdiaphragmatic pressure. Unloading caused a 57 percent reduction of the inspiratory transdiaphragmatic pressure-time product (p<0.05), while tidal volume, breathing frequency, and breathing pattern did not significantly change. These observations suggest that during increased ventilatory requirements, PAV results in down regulation of respiratory muscle activity and that this effect is mainly a consequence of neuromechanical inhibition.

Background: The presence of a T-cell response to the early secretory antigenic target-6 (ESAT-6) indicates previous infection with or exposure to Mycobacterium tuberculosis. Measuring this response is useful for identifying individuals infected with M. tuberculosis. It was also reported that the frequencies of ESAT-6-specific T cells correlate with disease state. Established procedures measure secreted T-cell cytokines following whole blood stimulation with recombinant ESAT-6 protein or use Elispot as a read-out., Methods: A single ESAT-6- spanning pool of overlapping peptides (15 amino acids length with 11 overlaps) was used for overnight stimulation of peripheral blood mononuclear cells (PBMCs) from 15 patients infected with Mycobacterium tuberculosis and 11 healthy controls. T-cell responses were rated positive if interferon-gamma (IFN-gamma)-producing T cells were identified above background level, using 4-color cytokine flow cytometry., Results: Thirteen of 15 (87%) patients, but none of the healthy controls, had a positive CD4 T-cell response to the ESAT-6 spanning peptide pool. The frequencies of IFN-gamma-producing cells varied between 1 and 167 per 10,000 CD4 T cells. The test performed as well as the tests described in the literature., Conclusions: Cytokine flow cytometry following PBMC stimulation with an ESAT-6 spanning peptide pool is a useful laboratory test for ESAT-6-specific T cells combining precise counting and multi-parameter phenotyping., (Copyright 2004 Wiley-Liss, Inc.)

The newly identified 3p21.3 tumour suppressor gene RASSF1A is methylated in the majority of primary lung tumours, lung tumour cell lines and in a variable percentage of breast tumours. To determine the extent of RASSF1A promoter hypermethylation in early lung tumorigenesis, we analysed sputum samples from lung cancer patients and from current and former smokers using a sensitive methylation-specific PCR (MSP) technique. We also analysed RASSF1A promoter region hypermethylation in trios of normal breast/invasive ductal breast carcinoma/ductal carcinoma in situ (DCIS) from breast cancer patients and DCIS without invasive cancer. We found that 50% of small cell lung cancer (SCLC) and 21% of non-small cell lung cancer (NSCLC) patients had RASSF1A methylation, while one of two former smokers and four of 13 current smokers demonstrated RASSF1A methylation in sputum. Furthermore, two of the four current smokers and one former smoker showing RASSF1A methylation in their sputum developed cancer within 12-14 months of bronchoscopy. In our breast cancer trios, RASSF1A promoter hypermethylation was detected in 65% of invasive cancers, in 42% of corresponding DCIS but in none of the normal breast samples. In addition, we found that three out of 10 DCIS without invasive breast cancer also underwent RASSF1A promoter hypermethylation. Our findings suggest that RASSF1A promoter region hypermethylation may be a useful molecular marker for early detection of lung cancer. Furthermore, since RASSF1A promoter hypermethylation was detected in ductal carcinoma in situ, inactivation of RASSF1A may be an early event in breast tumorigenesis.

An 'enriched polymerase chain reaction (PCR)' protocol has been established for the sensitive detection of oncogene mutations in body fluid samples from cancer patients. This two-step protocol combines an allele-specific PCR clamping step followed by a PCR-RFLP (restriction fragment length polymorphism) confirmatory step. The method thus resembles a nested PCR technique starting directly from genomic DNA material and, in no more than 54 PCR cycles, allows the sensitive detection of one mutant allele in 10(3) normal alleles. This protocol was tested on bronchial cytology samples and sputum taken from lung cancer patients and point mutations could be detected both in codon 12 of K-ras and in three codons (248, 249, and 273) of the p53 gene. Comparing this protocol with a different 'enriched PCR' method based on repetitive PCR-RFLP steps, a high concordance was noted between the two methods. Although the present protocol seems to be less sensitive by approximately one order of magnitude, it is much easier to perform and thus could be applied to the rapid but sensitive detection of allelic subfractions in a population of cells derived from exfoliative material., (Copyright 2000 John Wiley & Sons, Ltd.)

Nocturnal gastro-oesophageal reflux has been observed in patients with obstructive sleep apnoea (OSA). Negative intrathoracic pressure during apnoeas and arousal have been suggested as the underlying mechanisms. In order to evaluate this hypothesis, the coincidence and sequence in time of arousal, apnoea and reflux events were analysed. Fifteen patients with OSA or heavy snoring were studied by means of standard polysomnograpy with parallel recording of 24-h oesophageal pH. Reflux events during the day were present in all patients, five of whom had symptoms of reflux. In three of these and in five other patients, a total of 69 nocturnal reflux events were found. In 68 events, arousal was found with the reflux event. Only one reflux without arousal was found (sleep stage 2). Seventeen events occurred during wakefulness after sleep onset. The percentage of time with a pH of <4 during wakefulness after sleep onset was significantly higher than the percentage of time with a pH of <4 during total sleep time (p<0.05). In 37 of the 52 reflux events which occurred during sleep, either an apnoea or a hypopnoea was found prior to the event. The investigation of sequence in time did not prove a causal relation between respiratory events and reflux events. The results indicate that gastro-oesophageal reflux and obstructive sleep apnoea are two separate disorders, which both have a high prevalence in obese patients.

RFLP-mediated PCR has been successfully applied as a reliable tool in the detection of ras mutations in many cancers and provides a basis for "mutant-enriched PCR" protocols. We have, therefore, modified this technique to the sensitive detection of K-ras codon 12 and also p53 "hot spot" mutations, which, frequently in lung cancer, affect codons at the positions 157, 175, 245, 248, 249, and 273. With a high sensitivity of 1 mutant allele in 10(4) normal alleles, our enrichment assay allows the detection of oncogene alleles when only a few tumor cells are present within a normal cell population. Brush cytology material obtained from the tumor site of 20 patients with endoscopically apparent bronchial carcinoma was compared to macroscopically normal mucosa taken from the contralateral bronchus ("control" cytology). We found K-ras codon 12 mutations in 5 cases (25%) and p53 mutations in 13 cases (65%) in the tumor-derived cell material but, with the exception of two cases, not in cell material taken from the control cytology. Seventy-five % of the samples analyzed showed that at least one of the two oncogenes was affected. In several cases, two p53 lesions were detected concomitantly. The majority of the mutations could be reconfirmed by an alternative approach exploiting changes in the genomic RFLP pattern induced by these mutations and were also demonstrated in separate diagnostic biopsies taken. Thus, we conclude that the established enriched PCR protocol ensures a high sensitivity and preserved specificity for the diagnosis of oncogene lesions associated with lung cancer. Because conventional techniques normally yield a lower incidence of corresponding ras and p53 mutations, we think that both the high rate and the heterogeneity of p53 mutations found in some cases are, indeed, related to the increased sensitivity of this new enriched PCR technique.

Heart block during sleep has been described in up to 10% of patients with obstructive sleep apnoea. The aim of this study was to determine the relationship between sleep stage, oxygen desaturation and apnoea-associated bradyarrhythmias as well as the effect of nasal continuous positive airway pressure (nCPAP)/nasal bi-level positive airway pressure (nBiPAP) therapy on these arrhythmias in patients without electrophysiological abnormalities. Sixteen patients (14 males and two females, mean age 49.6+/-10.4 yrs) with sleep apnoea and nocturnal heart block underwent polysomnography after exclusion of electrophysiological abnormalities of the sinus node function and atrioventricular (AV) conduction system by invasive electrophysiological evaluation. During sleep, 651 episodes of heart block were recorded, 572 (87.9%) occurred during rapid eye movement (REM) sleep and 79 (12.1%) during nonrapid eye movement (NREM) sleep stages 1 and 2. During REM sleep, the frequency of heart block was significantly higher than during NREM sleep: 0.69+/-0.99 versus 0.02+/-0.04 episodes of heart block x min(-1) of the respective sleep stage (p<0.001). During apnoeas or hypopnoeas, 609 bradyarrhythmias (93.5%) occurred with a desaturation of at least 4%. With nCPAP/ nBiPAP therapy, apnoea/hypopnoea index (AHI) decreased from 75.5+/-39.6 x h(-1) to 3.0+/-6.6 x h(-1) (p<0.01) and the number of arrhythmias from 651 to 72 (p<0.01). We conclude that: 1) 87.9% of apnoea-associated bradyarrhythmias occur during rapid eye movement sleep; 2) the vast majority of heart block episodes occur during a desaturation of at least 4% without a previously described threshold value of 72%; and 3) nasal continuous positive airway pressure or nasal bi-level positive airway pressure is the therapy of choice in patients with apnoea-associated bradyarrhythmias.

Noninvasive positive pressure ventilation (NPPV) can improve ventilation in obese subjects during the postoperative period after abdominal surgery. Compared to nasal continuous positive airway pressure (nCPAP), NPPV was superior in correcting blood gas abnormalities both during the night-time and during the daytime in a subgroup of patients with the obesity hypoventilation syndrome (OHS). However, as it is unknown, if and to what extent NPPV can unload the respiratory muscles in the face of the increased impedance of the respiratory system in obesity, this is what was investigated. Eighteen obese subjects with a body mass index > or = 40 kg x m(-2) were investigated during the daytime, which included five healthy controls (simple obesity (SO)), seven patients with obstructive sleep apnoea (OSA) and six patients with the obesity hypoventilation syndrome (OHS). Assisted PPV was performed with bi-level positive airway pressure (BiPAP), applied via a face mask. Inspiratory positive airway pressure (IPAP) was set to 1.2 or 1.6 kPa and expiratory positive airway pressure (EPAP) was set to 0.5 kPa. Inspiratory muscle activity was measured as diaphragmatic pressure time product (PTPdi). Comparison of spontaneous breathing with BiPAP ventilation showed no significant difference in breathing pattern, although there was a tendency towards an increase in tidal volume (VT) in all three groups and a decrease in respiratory frequency (fR) in patients with OSA and OHS. End-tidal carbon dioxide (PET,CO2) with BiPAP was unchanged in SO and OSA, but was decreased in OHS. In contrast, inspiratory muscle activity was reduced by at least 40% in each group. This was indicated by a decrease in PTPdi with BiPAP 1.2/0.5 kPa from mean+/-SD 39+/-5 to 20+/-9 kPa x s (p<0.05) in SO, from 42+/-7 to 21+/-8 kPa x s (p<0.05) in OSA, and from 64+/-20 to 38+/-17 kPa x s (p<0.05) in OHS. With BiPAP 1.6/0.5 kPa, PTPdi was further reduced to 17+/-6 kPa x s in SO, and to 17+/-6 kPa x s in OSA, but not in OHS (40+/-22 kPa x s). We conclude that noninvasive assisted ventilation unloads the inspiratory muscles in patients with gross obesity.

Objective: To study the influence of obstructive sleep apnea (OSA) on 24-h BP., Setting: Sleep laboratory of the Medical Department, Neukölln Hospital, Berlin, Germany., Methods: In 93 subjects, noninvasive 24-h BP monitoring was performed with BP recordings made at 15-min intervals. Apnea severity was evaluated by means of a portable device that allows calculation of an oxygen desaturation index (ODI). A normal 24-h BP profile (dipping) was defined by a night/day BP ratio of 0.9., Results: ODI was related to systolic and diastolic daytime (p<0.001) and nighttime BP (p<0.001) as well as systolic and diastolic BP night/day ratios (p<0.001). Multiple regression analysis showed that age and ODI were independently related to daytime BP. When subjects were grouped according to apnea severity, daytime BP increased as ODI increased: 127/80+/-10/11 mm Hg in habitual snorers (ODI 0 to 5), 135/87+/-15/9 mm Hg in mild OSA (ODI 6 to 30), and 140/90+/-13/10 mm Hg in severe OSA (ODI >30) (p values <0.05 for comparisons of OSA groups with habitual snorers). Compared to subjects with mild OSA or habitual snorers, BP night/day ratios were greater in patients with severe OSA (p values <0.05). Accordingly, hypertension and nondipping increased as ODI increased., Conclusion: OSA is associated with hypertension independent of the confounding factors of age and obesity. Nondipping is related to apnea severity. These alterations might contribute to the increased mortality in patients with severe OSA.

We studied 24-h blood pressure (BP) in 17 hypertensive patients with polysomnographic verified moderate to severe obstructive sleep apnea (OSA) before, after 1-3 days and after 4-6 months of treatment with nasal continuous positive airway pressure (nCPAP). BP was recorded using an ambulatory blood pressure monitoring (ABPM) device with oscillometric measurement method (SpaceLabs 90207) over a period of 24 h with intervals of 15 min in daytime and nighttime. Hypertension was defined as mean BP in the daytime period > 135/85 mm Hg; OSA was diagnosed when a full night polysomnography indicated an apnea hypopnea index (AHI) > 10/h. Hypertensive systolic/diastolic daytime BP values decreased significantly from 144.8/94.4 mm Hg at baseline to 138.9/89.4 mm Hg after short-term, and to 136.4/86.9 mm Hg after long-term nCPAP-therapy. Nighttime BP values, too, were reduced significantly from 137.6/87.1 mm Hg at baseline to 129.9/82.3 mm Hg after short-term, and to 128.6/ 79.8 mm Hg after long-term therapy. In addition to these data the heart rate fell significantly from 82.5 b/min to 74.8 b/min after 4-6 months in daytime, and from 70.9 b/min to 63.6 b/min in nighttime. The beneficial effect on diurnal and nocturnal hypertension in patients with nCPAP-therapy of OSA suggests a causal relationship between systemic hypertension and obstructive sleep apnea.

Investigations were carried out to test the efficacy of a two dose treatment with ivermectin or doramectin on reactivated larvae of Toxocara canis in bitches to prevent prenatal and galactogenic infections of their pups. Thirty pregnant bitches were treated by subcutaneous injection of ivermectin or doramectin on day 40 and 50 post conception (p.c.) each with a dose of 1 mg/kg body weight. The efficacy of the treatments was determined by faecal examinations and by comparing the number of infected pups and the onset of patency in each group of pups. 1. Patient infections with T. canis were seen in pups from untreated bitches from day 21 after birth and all pups were coproscopically positive one week later. To prevent severe clinical symptoms all pups in this group were treated with anthelmintics on day 42 after birth. 2. Pups from ivermectin treated bitches occasionally exhibited patent infections from day 28 after birth onwards; pups from doramectin group exhibited infections from day 56 after birth. The number of patently infected pups in both groups increased till 70 days after birth, probably because of postnatal infections. 3. 28 days after parturition, T. canis infections became patent in all untreated bitches. Single bitches in the ivermectin and doramectin groups developed patent infections after day 49 after parturition. All coproscopically positive bitches had patently infected pups in their litters. 4. The contamination of the environment with eggs of T. canis was calculated from the results of the faecal examinations.(ABSTRACT TRUNCATED AT 250 WORDS)

To investigate the influence of cigarette smoking on alveolar macrophages (AM) we compared morphologic and immunocytochemic characteristics of bronchoalveolar lavage cells collected from 10 smokers and 8 nonsmokers. AM were studied using single cell fluorescence photometry. AM of smokers were larger in size (p < 0.001), showed stronger autofluorescence (p < 0.001), and expressed fewer HLA-DR antigens (p < 0.001) compared with AM of nonsmokers. AM of smokers were more heterogeneous in respect to cell size, autofluorescence, and HLA-DR antigen expression. HLA-DR antigen density on AM of smokers was independent of cell size and autofluorescence. This suggests that tobacco smoke reduces HLA-DR antigen expression in AM of different maturational states and that this defective expression of HLA class II antigens is not dependent on the amount of phagocytosed autofluorescent tobacco particles.

The expression of HLA class II genes is essential to the antigen-presenting function of monocytes and macrophages. With a new cytofluorometric method of single-cell analysis we investigated the density of HLA-DR antigen expression on alveolar macrophages (AM) of smokers. Although all AM of nonsmokers (100 +/- 1%) expressed HLA-DR antigens, only 79 +/- 12% of AM from smokers showed positive findings (p less than 0.001). Furthermore, the antigen density of those cells expressing this antigen was significantly reduced in smokers (p less than 0.001). The defective expression of class II genes on AM of smokers might contribute to the impaired antigen-presenting function found by some previous investigators.

An immunofluorescence method for assaying membrane-bound antigens on individual alveolar macrophages (AM) collected by bronchoalveolar lavage (BAL) is described. Cells were labelled with FITC-conjugated anti-HLA-DR antibodies in a single (direct) step. Quantification of the fluorescence was performed by computer-assisted cytophotometry. Alveolar macrophages, especially when obtained from cigarette smokers, exhibited an autofluorescence which interfered with the measurement of specific fluorescence. The specific fluorescence was calculated by determination of total fluorescence in the wave-length optimal for FITC and the non-specific fluorescence in a different wavelength during a second measurement. Specificity and reproducibility testing confirmed the reliability of the method.

Salivary glands of various stages of the last larval instar of Chironomus tentans were quantitatively analyzed with respect to the expansion of their Balbiani rings (B1, B2, B3) by a fast green staining procedure as well as to the rate of synthesis of their secretory proteins (S1, S2, S3) by a scintillation counting procedure of electrophoretic fractions. The extent of expansion of B1, B2 and B3 correlates positively with the rate of synthesis of S3, S2 and S1, respectively. With B1 and S3 these parameters undergo a parallel and developmentally specific change being rather depressed in intermolt, and particularly in diapausing animals.