SAS CARE 2 - a randomized study of CPAP in patients with obstructive sleep disordered breathing following ischemic stroke or transient ischemic attack.

OBJECTIVE/BACKGROUND: The benefit of Continuous Positive Airway Pressure (CPAP) treatment following ischemic stroke in patients with obstructive sleep-disordered breathing (SDB) is unclear. We set out to investigate this open question in a randomized controlled trial as part of the SAS-CARE study. PATIENTS/METHODS: Non-sleepy patients (ESS < 10) with ischemic stroke or transient ischemic attack (TIA) and obstructive SDB (AHI ≥ 20) 3 months post-stroke were randomized 1:1 to CPAP treatment (CPAP+) or standard care. Primary outcome was the occurrence of vascular events (TIA/stroke, myocardial infarction/revascularization, hospitalization for heart failure or unstable angina) or death within 24 months post-stroke. Secondary outcomes included Modified Rankin Scale (mRS) and Barthel Index. RESULTS: Among 238 SAS-CARE patients 41 (17%) non-sleepy obstructive SDB patients were randomized to CPAP (n = 19) or standard care (n = 22). Most patients (80%) had stroke and were males (78%), mean age was 64 ± 7 years and mean NIHSS score 0.6 ± 1.0 (range: 0-5). The primary endpoint was met by one patient in the standard care arm (a new stroke). In an intent-to treat analysis disregarding adherence, this corresponds to an absolute risk difference of 4.5% or an NNT = 22. mRS and Barthel Index were stable and similar between arms. CPAP adherence was sufficient in 60% of evaluable patients at month 24. CONCLUSION: No benefit of CPAP started three months post-stroke was found in terms of new cardio- and cerebrovascular events over 2 years. This may be related to the small size of this study, the mild stoke severity, the exclusion of sleepy patients, the delayed start of treatment, and the overall low event rate.

A randomised, controlled trial evaluating a low cost, 3D-printed bronchoscopy simulator.

Low-fidelity, simulation-based psychomotor skills training is a valuable first step in the educational approach to mastering complex procedural skills. We developed a cost-effective bronchial tree simulator based on a human thorax computed tomography scan using rapid-prototyping (3D-print) technology. This randomised, single-blind study evaluated how realistic our 3D-printed simulator would mimic human anatomy compared with commercially available bronchial tree simulators (Laerdal® Airway Management Trainer with Bronchial Tree and AirSim Advance Bronchi, Stavanger, Norway). Thirty experienced anaesthetists and respiratory physicians used a fibreoptic bronchoscope to rate each simulator on a visual analogue scale (VAS) (0 mm = completely unrealistic anatomy, 100 mm = indistinguishable from real patient) for: localisation of the right upper lobe bronchial lumen; placement of a bronchial blocker in the left main bronchus; aspiration of fluid from the right lower lobe; and overall realism. The 3D-printed simulator was rated most realistic for the localisation of the right upper lobe bronchial lumen (p = 0.002), but no differences were found in placement of a bronchial blocker or for aspiration of fluid (p = 0.792 and p = 0.057) compared with using the commercially available simulators. Overall, the 3D-printed simulator was rated most realistic (p = 0.021). Given the substantially lower costs for the 3D-printed simulator (£85 (€100/US$110) compared with > ~ £2000 (€2350/US$2590) for the commercially available simulators), our 3D-printed simulator provides an inexpensive alternative for learning bronchoscopy skills, and offers the possibility of practising procedures on patient-specific models before attempting them in clinical practice.

Treatment failure in pneumonia: impact of antibiotic treatment and cost analysis.

The aim of this study was to investigate treatment failure (TF) in hospitalised community-acquired pneumonia (CAP) patients with regard to initial antibiotic treatment and economic impact. CAP patients were included in two open, prospective multicentre studies assessing the direct costs for in-patient treatment. Patients received treatment either with moxifloxacin (MFX) or a nonstandardised antibiotic therapy. Any change in antibiotic therapy after >72 h of treatment to a broadened antibiotic spectrum was considered as TF. Overall, 1,236 patients (mean ± SD age 69.6 ± 16.8 yrs, 691 (55.9%) male) were included. TF occurred in 197 (15.9%) subjects and led to longer hospital stay (15.4 ± 7.3 days versus 9.8 ± 4.2 days; p < 0.001) and increased median treatment costs (€2,206 versus €1,284; p<0.001). 596 (48.2%) patients received MFX and witnessed less TF (10.9% versus 20.6%; p < 0.001). After controlling for confounders in multivariate analysis, adjusted risk of TF was clearly reduced in MFX as compared with ß-lactam monotherapy (adjusted OR for MFX 0.43, 95% CI 0.27-0.68) and was more comparable with a ß-lactam plus macrolide combination (BLM) (OR 0.68, 95% CI 0.38-1.21). In hospitalised CAP, TF is frequent and leads to prolonged hospital stay and increased treatment costs. Initial treatment with MFX or BLM is a possible strategy to prevent TF, and may thus reduce treatment costs.

[The impact of viruses in lower respiratory tract infections of the adult. Part III: therapy and prevention]. / Die Rolle von Viren bei tiefen Atemwegsinfektionen des Erwachsenen. Teil 3: Therapie und Prävention.

In industrialized countries respiratory tract infections are one of the most common reasons for medical consultations. It is assumed that almost one third of these infections include the lower respiratory tract (LRTI), e. g. acute bronchitis, acute exacerbation of chronic obstructive pulmonary disease (COPD), community- or hospital-acquired pneumonia and influenza. Due to a lack of sufficient and valid investigations to prove the presence of respiratory viruses their impact in the pathogenesis of lower respiratory tract infection has probably been underestimated for a long time. Therefore, there might have been many cases of unnecessary antibiotic treatment, especially in cases of acute bronchitis or acute exacerbations of COPD, because of an assumed bacteriological cause. With the introduction of more sensitive investigational procedures, such as polymerase chain reaction, it is possible to sufficiently prove respiratory viruses and therefore illuminate their role in the pathogenesis of lower respiratory tract infections of the adult. We have reviewed the current literature on the impact of viruses in lower respiratory tract infections to elucidate the role of viruses in the pathogenesis of lower respiratory tract infections. The preceding parts of this series provided an introduction to the frequently found viruses, pathogenesis, and diagnostic procedures (part I) as well as common viral infections of the lower respiratory tract (part II). The present 3 (rd) part deals with therapy for and prevention of viral LRTI.

[The impact of viruses in lower respiratory tract infections of the adult. Part II: acute bronchitis, acute exacerbated COPD, pneumonia, and influenza]. / Die Rolle von Viren bei tiefen Atemwegsinfektionen des Erwachsenen. Teil 2: Akute Bronchitis, exazerbierte COPD, Pneumonie und Influenza.

In industrialized countries respiratory tract infections are one of the most common reasons for medical consultations. It is assumed that almost one third of these infections affect the lower respiratory tract (LRTI), e. g. acute bronchitis, acute exacerbation of chronic obstructive pulmonary disease (COPD), community- or hospital-acquired pneumonia and influenza. Due to a lack of sufficient and valid investigations on the epidemiology of respiratory viruses, their impact on the pathogenesis of LRTI has probably been underestimated for a long time. Therefore, there might have been many cases of needless antibiotic treatment, particularly in cases of acute bronchitis or acute exacerbations of COPD, because of an assumed bacteriological aetiology. Following the introduction of diagnostic procedures with increased sensitivity, such as polymerase chain reaction, it is possible to reliably detect respiratory viruses and to illuminate their role in the pathogenesis of LRTI of the adult. We have reviewed the current literature to elucidate the role of viruses in the pathogenesis of LRTI. The first part of this series described frequent viral pathogens, pathogenesis of viral LRTI, and diagnostic procedures. In this 2 (nd) part the aetiological role of viruses in the most frequent forms of LRTI will be highlighted, and the third and last part will provide an overview of therapeutic and preventive options.

[The impact of viruses in lower respiratory tract infections of the adult. Part I: Pathogenesis, viruses, and diagnostics]. / Die Rolle von Viren bei tiefen Atemwegsinfektionen des Erwachsenen. Teil 1: Erreger, Pathogenese und Diagnostik.

In industrialised countries respiratory tract infections are one of the most common reasons for medical consultations. It is assumed that almost one third of these infections include the lower respiratory tract (LRTI), e. g. acute bronchitis, acute exacerbation of chronic obstructive pulmonary disease (COPD), community- or hospital-acquired pneumonia and influenza. Due to a lack of sufficient and valid investigations on the epidemiology of respiratory viruses, their impact on the pathogenesis of LRTI has probably been underestimated for a long time. Therefore, there might have been many cases of needless antibiotic treatment, particularly in cases of acute bronchitis or acute exacerbations of COPD, because of an assumed bacteriological aetiology. Following the introduction of diagnostic procedures with increased sensitivity, such as polymerase chain reaction, it is possible to reliably detect respiratory viruses and to illuminate their role in the pathogenesis of LRTI of the adult. We have reviewed the current literature to elucidate the role of viruses in the pathogenesis of LRTI. The first part of this series deals with the relevant pathogens, pathogenesis, and diagnostic procedures. In the subsequent 2 parts of this series a review will be given on the most common variants of viral LRTI (part II), and therapeutic and preventive options (part III).

Moxifloxacin vs ampicillin/sulbactam in aspiration pneumonia and primary lung abscess.

BACKGROUND: Aspiration pneumonia (AP) and primary lung abscess (PLA), are diseases following aspiration of infectious material from the oropharynx or stomach. An antibiotic therapy, also covering anaerobic pathogens, is the treatment of choice. In this study we compared moxifloxacin (MXF) and ampicillin/sulbactam (AMP/SUL) concerning efficacy and safety in the treatment of AP and PLA. METHODS: Patients with pulmonary infections following aspiration were included in a prospective, open-label, randomized, multicenter trial. Sequential antibiotic therapy with MXF or AMP/SUL was administered until complete radiologic and clinical resolution. RESULTS: A total of 139 patients with AP and PLA were included, 96 were evaluable for efficacy (EE, 48 patients in each treatment group). The overall clinical response rates in both groups were numerically identical (66.7%). MXF and AMP/SUL were both well tolerated, even after long-term administration [median duration of treatment (range) in days MXF versus AMP/SUL: AP 11 (4-45) vs 9 (3-25), PLA 30.5 (7-158) vs 35 (6-90)]. CONCLUSION: In the treatment of aspiration-associated pulmonary infections moxifloxacin appears to be clinically as effective and as safe as ampicillin/sulbactam; but, however, having the additional benefit of a more convenient (400 mg qd) treatment.

[Diagnosis and therapy of aspiration pneumonia]. / Diagnostik und Therapie der Aspirationspneumonie.

Aspiration pneumonia is an important and frequent complication following aspiration of infectious material from the oropharynx or stomach. Therefore the microbiological flora generally comprises a mixed spectrum of microbes including aerobic, microaerobic and anaerobic mircoorganisms. There are a number of risk factors for aspiration such as compromised consciousness or esophageal diseases. Aspiration pneumonia presents as a subacute or chronic disease. An endoscopic inspection of the bronchial system and a bacteriological evaluation should be performed in all patients. The principal therapeutic strategy for aspiration pneumonia is an antibiotic therapy. In uncomplicated cases a treatment for 7-10 days should be sufficient, but in case of complications like necrotizing pneumonia or lung abscess a prolonged administration (14-21 days, up to weeks or months) will be necessary. Recommended antibiotic regimens include clindamycin +/- cephalosporin, ampicillin/sulbactam and moxifloxacin.

GABA-like immunoreactivity in nonspiking interneurons of the locust metathoracic ganglion.

Nonspiking interneurons are important components of the premotor circuitry in the thoracic ganglia of insects. Their action on postsynaptic neurons appears to be predominantly inhibitory, but it is not known which transmitter(s) they use. Here, we demonstrate that many but not all nonspiking local interneurons in the locust metathoracic ganglion are immunopositive for GABA (gamma-aminobutyric acid). Interneurons were impaled with intracellular microelectrodes and were shown physiologically to be nonspiking. They were further characterized by defining their effects on known leg motor neurons when their membrane potential was manipulated by current injection. Lucifer Yellow was then injected into these interneurons to reveal their cell bodies and the morphology of their branches. Some could be recognised as individuals by comparison with previous detailed descriptions. Ganglia were then processed for GABA immunohistochemistry. Fifteen of the 17 nonspiking interneurons studied were immunopositive for GABA, but two were not. The results suggest that the majority of these interneurons might exert their well-characterized effects on other neurons through the release of GABA but that some appear to use a transmitter other than GABA. These nonspiking interneurons are therefore not an homogeneous population with regard to their putative transmitter.

Sensory afferents and motor neurons as targets for nitric oxide in the locust.

In the adult locust, nitric oxide (NO) synthase is expressed in interneurons that innervate mechanosensory neuropils, indicating that NO may participate in mechanosensory processing. Here, we have identified potential neuronal targets of NO by localizing the expression and activity of soluble guanylyl cyclase (SGC), its principal molecular target in the nervous system. We used two complementary approaches, namely immunolocalization of SGC alpha-subunit (SGCalpha), and of cyclic GMP (cGMP) after exposure to an NO donor. The cell bodies, axons and central projections of thoracic exteroceptors, proprioceptors, auditory receptors, and chemoreceptors were strongly immunoreactive for SGCalpha. Strong SGCalpha immunoreactivity also occurred in all thoracic motor neurons, including their axon terminals. NO-donors induced a pattern of cGMP immunostaining that was similar to the distribution of SGCalpha, indicating that both sensory and motor neurons contain functional SGC. Therefore, NO may modulate both the input from these sensory neurons and the output of motor neurons. Although the expression of SGCalpha was highly consistent, NO donors did not always induce cGMP-staining in SGC-containing neurons, suggesting that SGC is coregulated by factors other than NO. Complementing previous reports in the visual and olfactory system, our results indicate a general role for NO-cGMP signaling in early sensory processing; diffusible signals may mediate a cross-adaptation or -sensitization within neural maps where similarly tuned neurons have adjacent projections, an anatomical arrangement shared by many sensory systems.

NADPH diaphorase histochemistry in the thoracic ganglia of locusts, crickets, and cockroaches: species differences and the impact of fixation.

The NADPH diaphorase (NADPHd) reaction is widely used as a histochemical marker for nitric oxide synthase (NOS). In this study on locusts, crickets, and cockroaches, we demonstrate 1) that related species can differ considerably in the fixation sensitivity of putatively NOS-related NADPHd; and 2) that prolonged fixation can induce NADPHd activity in cells that are diaphorase negative under mild fixation regimes. These two phenomena reconcile previous, contradictory reports on the distribution of NADPHd in locusts and crickets. In locusts, neuronal NADPHd is found exclusively in interneurones. The projection neuropiles of the exteroceptors contain a dense NADPHd-positive fibre meshwork, but sensory afferents do not stain. In crickets, staining has been reported in sensory afferents, in motor neurones and dorsal unpaired median (DUM) neurones, and in a non-fibrous distribution throughout the sensory neuropiles. We demonstrate that this widespread, non-selective staining is induced by strong formaldehyde fixation. Weak fixation resulted in a highly selective labelling of a few individual interneurones and of a fibre meshwork in the projection neuropiles of the exteroceptive afferents. Staining was absent in the afferents themselves, in motor neurones, and in efferent DUM neurones. Thus, after weak fixation, the staining pattern closely matched that in the locust. The similar distribution of putatively NOS-related NADPHd in the thoracic nervous systems of orthopteroid insects suggests a species-independent role for nitric oxide in the processing of mechanosensory information. Histopharmacological techniques such as permanganate oxidation, or incubation in the NOS inhibitors methylene blue or dichlorophenolindophenol, did not allow discrimination between the selective and the fixation-induced staining. The species-specific impact of different fixation regimes may necessitate reconsideration of results obtained in other cross-species comparisons.

Nitric oxide synthase in the thoracic ganglia of the locust: distribution in the neuropiles and morphology of neurones.

Nitric oxide signaling is implicated in olfactory and visual pathways within the insect brain. In contrast, little is known about the distribution and function of nitric oxide synthase (NOS) in the ventral nerve cord. This study uses NADPH diaphorase histochemistry to describe the anatomy of NOS-containing neurones and the neuropilar distribution of NOS in the thoracic nerve cord of the locust. It is shown for the first time that mechanosensory neuropiles receive innervation from NOS-containing interneurones. Different cells innervate exteroceptive and proprioceptive projection neuropiles. In the projection neuropiles of tactile afferents, a dense meshwork of NOS-containing fibres is formed by collaterals of paired intersegmental axons that run through the entire thoracic nerve cord, innervating exclusively these exteroceptive neuropiles. In neuropile areas where proprioceptive afferents terminate, stained fibres are comparatively sparse and originate from local interneurones. The prothoracic ganglion showed strongly stained dense fibres in the dorsal neuropile that were not seen in the other neuromeres. This differential NOS-expression can be related to the branching pattern of a ventral group of neurones that was different in each neuromere. All thoracic neuromeres and the abdominal neuromeres A2 and A3 of the metathoraic ganglion contained a previously undescribed type of unpaired median neurone with bilaterally ascending and descending intersegmental projections that stained strongly for NOS. The distribution of NOS found in this study suggests a novel role for nitric oxide in an early stage of mechanosensory information processing in all thoracic neuromeres and an additional role in the prothoracic ganglion, which might be related to behavioural specializations of the forelegs.

Acquisition of high-resolution digital images in video microscopy: automated image mosaicking on a desktop microcomputer.

For the digital processing of microscopical images, mosaicking is a prerequisite if the specimen is larger than the camera field at the necessary magnification. This study investigates the possibilities and limitations of fully automated mosaicking on a desktop computer. Cross-correlation-based frame registration was performed with high reliability if the video frames were edge-enhanced before matched filtering, and also in a reasonable time since the search for matches was restricted to pairs of consecutive frames. An environment for routine mosaicking was developed and implemented in a widely used desktop image-processing program. The software developed during this study has been released to the public domain.