Outcome of community-acquired pneumonia: influence of age, residence status and antimicrobial treatment.

Community-acquired pneumonia remains a major cause of mortality in developed countries. There is much discrepancy in the literature regarding factors influencing the outcome in the elderly population. Data were derived from a multicentre prospective study initiated by the German Competence Network for Community-Acquired Pneumonia. Patients with community-acquired pneumonia (n = 2,647; 1,298 aged < 65 yrs and 1,349 aged > or = 65 yrs) were evaluated, of whom 72.3% were hospitalised and 27.7% treated in the community. Clinical history, residence status, course of disease and antimicrobial treatment were prospectively documented. Microbiological investigations included cultures and PCR of respiratory samples and blood cultures. Factors related to mortality were included in multivariate analyses. The overall 30-day mortality was 6.3%. Elderly patients exhibited a significantly higher mortality rate that was independently associated with the following: age; residence status; confusion, urea, respiratory frequency and blood pressure (CURB) score; comorbid conditions; and failure of initial therapy. Increasing age remained predictive of death in the elderly. Nursing home residents showed a four-fold increased mortality rate and an increased rate of gram-negative bacillary infections compared with patients dwelling in the community. The CURB score and cerebrovascular disease were confirmed as independent predictors of death in this subgroup. Age and residence status are independent risk factors for mortality after controlling for comorbid conditions and disease severity. Failure of initial therapy was the only modifiable prognostic factor.

[Antibiotic therapy for exacerbation]. / Antibiotikatherapie bei Exazerbation.

Bacterial infections are involved in approximately 50% of acute exacerbations of chronic bronchitis (AECB). Pneumococci, Haemophilus influenzae and Moraxella catarrhalis are the main pathogens. Studies using quantitative cultures and molecular typing suggest a causal relationship between bacterial infection and exacerbation. Furthermore, an association between infection and bronchial inflammation has been demonstrated. In contrast to steroid therapy and non-invasive ventilation, the benefits of antibiotic treatment are not well established. Current guidelines recommend antimicrobial therapy for AECB in type I exacerbations, for patients needing ventilatory support and for patients with cardiac comorbidity. Bacterial eradication is able to prolong the infection free interval.

Enhanced PMN response in chronic bronchitis and community-acquired pneumonia.

Chronic bronchitis is a frequent underlying disease in community-acquired pneumonia (CAP). It is unclear to what extent an impaired or exaggerated innate immune response contributes to disease manifestations and severity. To assess the role of neutrophil activation and recruitment during acute pneumonic episodes, peripheral polymorphonulcear neutrophil (PMN) activation, chemotactic activity, interleukin-8 (CXCL-8) and CXCL-8 receptor (CXCR) expression and apoptosis rate were evaluated in CAP patients with and without chronic bronchitis. In addition, the expression of CXCRs and CXCL-8 was assessed on pulmonary neutrophils in chronic bronchitis patients to compare the activation of the chemokine system in different compartments. CAP severity was assessed by the simplified acute physiology score II and the prognosis of disease was assessed by the pneumonia severity index (PSI). An increased chemotactic activity of PMN from chronic bronchitis patients with CAP was found, which was not related to the expression of CXCRs. In addition, a decreased apoptosis rate of PMN was observed. Chemotactic activity was related to the PSI. Comparison of peripheral and pulmonary PMN revealed enhanced CXCL-8 levels and a decreased CXCR expression in the lung. In conclusion, neutrophil function in patients with chronic bronchitis and community-acquired pneumonia is characterised by an increased chemotactic activity combined with a decreased apoptosis rate. The downregulation of interleukin-8 receptors in the pulmonary compartment deserves further investigation.

Imbalanced secretion of IL-1beta and IL-1RA in Chlamydia pneumoniae-infected mononuclear cells from COPD patients.

Balanced secretion of pro- and anti-inflammatory cytokines is essential in limiting pulmonary inflammation in respiratory infections. It was hypothesised that, in acute infection with Chlamydia pneumoniae, mononuclear cells from chronic obstructive pulmonary disease (COPD) patients lack the opportunity to compensate for the inflammatory immune response by secreting adequate amounts of anti-inflammatory cytokines. Alveolar macrophages (AMs) and peripheral blood mononuclear cells (PBMCs) from eight COPD patients and eight healthy controls were infected with C. pneumoniae in order to determine interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1RA) and IL-8 expression and messenger ribonucleic acid levels. Secretion of IL-1beta was significantly enhanced in AMs (six-fold) and PBMCs (four-fold) from COPD patients after infection with C. pneumoniae. Compared to the control group, release of its anti-inflammatory counterpart IL-1RA was diminished in COPD patients, resulting in a significantly higher IL-1beta/IL-1RA ratio in C. pneumoniae-infected AMs and PBMCs from COPD patients. Mononuclear cells from chronic obstructive pulmonary disease patients have less capacity for balancing the pro-inflammatory immune response caused by Chlamydia pneumoniae infection than those from healthy controls. These findings suggest that, during acute exacerbation with intracellular pathogens, chronic obstructive pulmonary disease patients are predisposed to inflammatory changes in the lungs.

[Infection hypothesis of coronary heart disease]. / Die Infektionshypothese der koronaren Herzkrankheit.

It is well accepted that coronary artery disease is linked to an inflammatory process. It is unproven however whether either infectious agents may cause or accelerate coronary artery disease or the inflammatory process is due to metabolic or toxic effects. Among the possible infectious agents Chlamydia pneumoniae is the most likely bacterium involved in atherosclerosis. The arguments in favour of Chlamydia pneumoniae originate from seroepidemiologic studies and from detection and isolation of bacteria from vascular lesions. This review summarises the present understanding of the role of bacterial infection for development or progression of coronary artery disease.

Strategies for structure solution and refinement of small organic molecules from electron diffraction data and limitations of the simulation approach

In recent years, a series of non-linear optically active bis(benzylidene) ketones have been synthesized and investigated by electron crystallography. In most cases, structure refinement was possible by combining electron diffraction analysis and quantum-mechanical calculations with maximum-entropy methods. However, when the torsional angles between the phenyl rings and the C=C double bonds are strongly affected by the crystal field, this method fails because packing-energy calculations are not sufficiently sensitive. This problem can be solved by refining the approximate model with SHELXL, if the data set is sufficiently accurate and the model close to the correct structure. Here it is shown that a considerably superior data set can be obtained at 300 kV with on-line data acquisition.

Comparison of electron diffraction data from non-linear optically active organic DMABC crystals obtained at 100 and 300 kV

During the recent past, we have synthesized a new class of molecules with intramolecular two-dimensional charge transfer upon excitation. The present report presents such a molecule, 2,6-bis(4-dimethylamino-benzylidene)-cyclohexanone (DMABC), with an unusually high value of the second-order non-linear optical (NLO) coefficients. In order to optimize the macroscopic NLO properties of the compounds, it is necessary to relate their first hyperpolarizability tensors at a molecular level to those at a crystal bulk level. This requires a complete structure determination and refinement. However, the growth of sufficiently large single crystals, which are needed for structural analysis and refinement by X-ray methods, is a time consuming and sometimes impossible task. We have performed a complete structural analysis by electron diffraction combined with simulation methods and with maximum entropy and log likelihood statistics. In order to improve the quantitative analysis, a 300 kV data set using an on-line CCD camera was added and the best attainable R-values were compared with those from 100 kV data using film emulsions. Details regarding the maximum attainable resolution for both data sets are discussed as well as the problems which arise from the limited dynamic range in photographic emulsions as compared to a 14 bit CCD camera. Once the crystal structure was known, quantum-chemical methods were used to calculate non-linear optical susceptibility tensor components and these were related to the macroscopic coefficients of the crystalline quadratic non-linearity tensor. In the present work, both ab initio and semi-empirical quantum-chemical calculations were employed.

Hydroxymethylglutaryl coenzyme A reductase inhibitors modify the inflammatory response of human macrophages and endothelial cells infected with Chlamydia pneumoniae.

BACKGROUND: In patients with atherosclerosis, hepatic hydroxymethylglutaryl coenzyme A reductase (CSE) inhibitors may reduce the activation of inflammation. Because Chlamydia pneumoniae infection has been linked to coronary artery disease through the induction of plaque inflammation, we investigated whether cerivastatin affects the infection rate of human macrophages and endothelial cells (ECs) and their proinflammatory activation after chlamydial infection. METHODS AND RESULTS: Macrophages were collected from the alveolar compartment of 6 volunteers and 10 patients with chronic bronchitis. ECs were obtained from 10 umbilical cords. The C. pneumoniae strain CWL was incubated with macrophages or ECs in the presence and absence of the CSE inhibitor cerivastatin. The infection rate was determined by immunofluorescence microscopy. The release of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), and tumor necrosis factor (TNF)-alpha was quantified by ELISA. The release of oxygen radicals was determined by ferricytochrome assay. Infection rates were tendentially lower after the preincubation of macrophages with CSE inhibitors (17.2% versus 9. 3% and 18.2% versus 10.4%, respectively; P=NS). The secretion of MCP-1, IL-8, and TNF-alpha by infected macrophages from volunteers increased. Coincubation with cerivastatin resulted in significantly lower MCP-1 and IL-8 production, whereas the release of TNF-alpha remained unaffected. Similar effects regarding chemokine release were observed in ECs. CONCLUSIONS: CSE inhibitors modify the inflammatory response of human immune cells to C. pneumoniae. This finding could be relevant for the therapeutic potential of CSE statins in patients with atherosclerosis and C. pneumoniae infection.

[Incidence of bacterial pneumonia in HIV-positive patients treated with preventive co-trimoxazole or pentamidine]. / Inzidenz bakterieller Pneumonien bei HIV-positiven Patienten unter Chemoprophylaxe mit Co-trimoxazol oder Pentamidin.

BACKGROUND: Besides Pneumocystis carinii bacterial pathogens represent the most common aetiology of pulmonary infections in HIV-positive patients. However, the impact of PCP prophylaxis on the incidence of bacterial pneumonia in HIV-positive patients using pentamidine or co-trimoxazole is still unknown. PATIENTS AND METHODS: We analysed retrospectively the data of 80 consecutive HIV-positive patients with a CD4-cell count < 300/microliter. The total observation period was 1993 patient months. Type and duration of chemoprophylaxis, frequency of bacterial pneumonia, PCP, extrapulmonary bacterial infections and cerebral toxoplasmosis were documented in a standardised manner. For statistical analysis we used the Kaplan-Meier test for the time to a recurrence of the various infections under both prophylaxis regimens and the Odds ratio for determination of the relative risk. RESULTS: We followed up 47 patients inhaling 300 mg pentamidine monthly for a total of 1133 months and 33 patients taking 480 mg co-trimoxazole per day p.o. for a total of 860 months. There were no statistically significant differences between the two groups in respect of demographic parameters, stage and therapy of HIV infection and distribution of risk groups. We found seven bacterial pneumonias in the co-trimoxazole group and 13 in the pentamidine group (not significant); the most common causative organisms were S. pneumoniae (n = 4), S. aureus (n = 3) and H. influenzae (n = 3). Furthermore, in the pentamidine group 12 PCP and nine cases of toxoplasma encephalitis were observed, whereas none of these infections occurred in the co-trimoxazole group (p < 0.05). Two of the patients taking co-trimoxazole and 15 of those inhaling pentamidine had extrapulmonary bacterial infections (p < 0.05), the most frequently identified pathogen being S. aureus (n = 7). The two prophylaxis groups did not differ significantly with regard to laboratory data, course and therapy of the bacterial pneumonias. CONCLUSION: There was no significant influence of chemoprophylaxis on the incidence of bacterial pneumonia in patients with advanced HIV-disease in our study. Since S. pneumoniae represents the most common causative agent, we suggest immunisation with a polyvalent pneumococcal vaccine at an early stage of HIV-infection.

[Pentoxifylline inhibits secretion of O2- and TNF-alpha by alveolar macrophages in patients with sarcoidosis]. / Pentoxifyllin hemmt die Sekretion von O2- und TNF-alpha durch Alveolarmakrophagen bei Patienten mit Sarkoidose.

Reactive oxygen species (ROS) and cytokines like tumor necrosis factor-alpha (TNF-alpha) play a crucial role as inflammatory mediators in pulmonary sarcoidosis. We examined the antiinflammatory effect of pentoxifylline (POF) on alveolar macrophages (AM) of patients with sarcoidosis in vitro. We could demonstrate that POF (above 4.10(-4) M) inhibited the secretion of superoxide anion and TNF-alpha by AM in a dose-dependent manner via a prostaglandin synthesis-dependent mechanism that was independent of the glucocorticoid receptor. POF is an interesting immunomodulating substance that should be further evaluated in clinical trials.

Oxidative metabolism of pulmonary phagocytes in acute pneumonia.

The oxidative response of activated phagocytes is a primary host defense mechanism in pneumonia, but is in addition capable of causing tissue damage. We evaluated amount and significance of the local oxidant production in immunocompetent and immunocompromised pneumonia patients; the relative contribution of neutrophils and alveolar macrophages to the total oxidant load was differentiated using chemiluminescence (CL) with different amplifiers. Luminol-enhanced CL correlated to neutrophil percentage and myeloperoxidase levels in the bronchoalveolar lavage and was markedly increased in both pneumonia groups. Lucigenin-enhanced CL was produced by both phagocyte types and not significantly increased. In both pneumonia groups elevated levels of serum proteins indicated severe alveolocapillary leakage. In conclusion the oxidative response in acute pneumonia was mainly due to neutrophil recruitment and activation; this defense mechanism was preserved even in severely immunocompromised patients.

[The effect of UV radiation on Trevira threads]. / Der Einfluss von UV-Bestrahlung auf Trevirafäden.

The UV sensitivity of trevira threads, which are used as material of loops in intraocular lenses, was examined under different conditions. Severe changes of the thread surface were induced by direct UV radiation without absorbing media. The in vitro alterations of the surface were smaller. The in vivo changes were unimportant and not clearly distinguishable from biological changes. Nevertheless, it is advisable for people using intraocular lenses to provide with short-wavelength filtration devices, such as absorptive spectacles.

[Clinical experiences with polyurethane soft foam fillings for retinal surgery]. / Klinische Erfahrungen mit Polyurethan-Weichschaumplomben für die Netzhautchirurgie.

Polyurethane sponge was used for scleral buckling in 165 patients suffering from retinal detachment. This material showed good tissue compatibility and the therapeutic procedure was successful in 90% of the cases thus treated. In 10 patients polyurethane was used with success for cerclage. Postoperative complications observed were infection of the sponge in one patient and conjunctival dehiscence in two. Polyurethane sponge is less elastic than silicone sponge but has the same scleral buckling effect.

[Animal experiment testing of polyurethane soft foam (SYSpur) as an episcleral filling material]. / Tierexperimentelle Testung von Polyurethan-Weichschaum (SYSpur) als episklerales Plombenmaterial.

Soft polyurethane foam was sutured to the sclerae of 28 rabbit eyes in a manner similar to scleral buckling in retinal detachment surgery. During the follow-up period no tissue incompatibility was observed and wound healing appeared to be without complications. Microscopic examination revealed fibrocytes growing through the sponge and after 24 weeks the polyurethane meshwork was completely filled with granulation tissue.

[Testing of polyurethane as an implant for its biological compatibility]. / Die Testung von Polyurethan als Implantat auf seine biologische Verträglichkeit.

A simple biological method is described for testing the biological compatibility of plastics without histological investigation. This is the implantation into the anterior chamber of the rabbit eye. The test material is polyurethane soft foam (SYSpur). It can be observed as biologically compatible. This result agreed with expert opinions on toxicity and histocompatibility.

[Cranio-cerebral injury and intraocular pressure]. / Schädel-Hirn-Trauma und Augeninnendruck.

In 102 patients with cranio-cerebral trauma the intra-ocular pressure was measured. Values of the intra-ocular pressure showed a falling tendency in patients with grade-I trauma during the first 5 days. On the 30th day normal values had been regained. In grade-II and III traumata starting readings were lower and rose again about 3 days after the injury. In no case a glaucoma could be traced. In 4 patients with grade III cranio-cerebral trauma the reaction of the intraocular pressure is similar to that occurring before death.

[Ophthalmologic complications in chronic inflammatory intestinal diseases]. / Ophthalmologische Komplikationen bei chronisch-entzündlichen Darmkrankheiten.

Through investigations which we performed ophthalmological complications in chronic inflammatory intestinal disease are revealed. It could be demonstrated that in most cases ocular symptoms are associated with joint troubles which in their turn depend on the severity of the general disease. Especially in elderly patients with longstanding history it is important to co-operate with representatives of other medical branches in the control of ocular complaints, since there may quickly occur functional deterioration when the eye is also involved.