Induction of direct antimicrobial activity through mammalian toll-like receptors.

The mammalian innate immune system retains from Drosophila a family of homologous Toll-like receptors (TLRs) that mediate responses to microbial ligands. Here, we show that TLR2 activation leads to killing of intracellular Mycobacterium tuberculosis in both mouse and human macrophages, through distinct mechanisms. In mouse macrophages, bacterial lipoprotein activation of TLR2 leads to a nitric oxide-dependent killing of intracellular tubercle bacilli, but in human monocytes and alveolar macrophages, this pathway was nitric oxide-independent. Thus, mammalian TLRs respond (as Drosophila Toll receptors do) to microbial ligands and also have the ability to activate antimicrobial effector pathways at the site of infection.

Ampicillin + sulbactam vs clindamycin +/- cephalosporin for the treatment of aspiration pneumonia and primary lung abscess.

Aspiration pneumonia, necrotising pneumonia and primary lung abscess are complications arising from the aspiration of infectious material from the oral cavity or stomach. There is limited information on optimal antibacterial therapeutic regimens. Patients with pulmonary infection following aspiration (n = 95) were included in a prospective, open, randomised, comparative multicentre trial to compare the safety, clinical and bacteriological efficacy of ampicillin + sulbactam vs. clindamycin +/- cephalosporin. Treated patients (n = 70) received sequential antibiotic therapy with either ampicillin + sulbactam (n = 37) or clindamycin (n = 33), with or without a second- or third-generation cephalosporin, administered until the complete resolution of clinical and radiological abnormalities. Definite or presumptive pathogens were isolated from 58 patients. Mean duration of therapy was 22.7 days for ampicillin + sulbactam and 24.1 days for clindamycin. In patients treated with ampicillin + sulbactam, the clinical response was 73.0% at the end of therapy and 67.5% 7-14 days after therapy. For clindamycin, the rates were 66.7% and 63.5%, respectively. Bacteriological response was similar in both treatment arms. Nine patients died (12.9%), with a Simplified Acute Physiology Score of > 30 points being the only significant predictive factor for therapeutic failure. Ampicillin + sulbactam and clindamycin +/- cephalosporin were both well-tolerated and proved equally effective in the treatment of aspiration pneumonia and lung abscess.

[Complications of nasal CPAP therapy. Consequences for general practice]. / Komplikationen bei der nasalen CPAP-Therapie. Konsequenzen für die Praxis.

BACKGROUND: The prevalence of the obstructive sleep apnea syndrome is about 5% in the entire population. The amount of treatment-indications grows for this particular sleep-related breathing disorder due to the increasing usage of diagnostic screening tests. In most cases, the positive-pressure ventilation, PPV (nCPAP, nBiPAP) is considered as a highly effective form of treatment, in comparison to other treating methods. The residential polysomnographic supervised adjustment of the treatment is optimally applied to most of the patients. Due to the increasing number of the treated patients, the reports about the appearance of short-termed side effects during the adjustment of the PPV become more frequent. PATIENTS AND RESULTS: We report on 9 patients who showed complications during the initial stage of treatment. The most common one, during the nCPAP-therapy, was the increase of central apneas. Because of this complication, a rapid optimization of the respiratory pressure or a change to a nBiPAP-therapy was necessary in 5 of the patients. 2 of the patients showed cardiac arrhythmias, some of which were severe. One patient produced a remarkable central hypoventilation during the initial phase of a nCPAP-therapy. The nBiPAP-titration combined with right-heart-catheter monitoring could demonstrate in another patient a possible cardiac decompensation through an increased ventilatory pressure. CONCLUSION: The risk of a positive-pressure ventilation is higher in patients with accompanying cardiac, pulmonary, neuropsychiatric and/or otorhinolaryngologic disorders. Considering the various predisposing factors of the patients we suggest an intensive apparative monitoring as well as stuff-supervision during the introduction to a respiratory treatment. If complications appear, a rapid improvement of the ventilatory pressure or a change to another respiratory treatment is indicated.

[Current approaches to smoking cessation]. / Aktuelle Strategien der Raucherentwöhnung.

Smoking causes about 5 Million deaths worldwide every year. Prevention and cessation of smoking should therefore be one of the most important public health priorities. The family doctor as a trusted contact and representative of the health care system plays an important role in this case. Smoking cessation can be achieved by a gradual cognitive-behavioral therapy which may be supported by pharmacotherapy. The continuous empathic support and motivation by the family doctor is however the most important factor. Even a small advance within this step-by-step strategy can be considered as a success which will be followed by further progress.

[Care and preventive experts lecture in the elementary school programme "Klasse2000" - co-operative teaching]. / Einsatz von Präventionsfachleuten im Grundschulprogramm Klasse2000 - Kooperativer Unterricht im Programm Klasse2000 -

In the context of the health promotion programme 'Klasse2000', 483 health experts gave specific lessons to pupils from the first to the fourth grade of the elementary school. Following the classes a survey was conducted as to the valuation of the programme, its translation into practice and co-operation between class teachers and health experts. Those questioned considered the programme as really applicable and were absolutely content with the organisation. They regarded direct working with pupils as fairly positive. Co-operation with class teachers was seen as ambivalent. The findings of this survey trigger further optimisation of the programme, especially to enlarge the time spent on efforts by the health experts and to intensify parent co-operation.

[Biopsy of thoracic space-occupying lesions--from computerized tomography to ultrasound-controlled puncture]. / Biopsie thorakaler Raumforderungen--Von der computertomographischen zur ultraschallgezielten Punktion.

PURPOSE: Having practised CT-controlled biopsies only, we introduced sonographically guided punctures since 1993 for pulmonary diagnoses. The effects are studied. METHOD: In a retrospective study 166 CT-guided biopsies from 1/89 to 12/95 and 50 sonographically guided biopsies from 7/93 to 12/95 were analysed. RESULTS: By CT, 67% intrapulmonary, 22% peripheral pulmonary and 11% pleuropulmonary, pleural and chest wall lesions were punctured. In 66% a diagnosis could be made. 13% of the patients experienced complications, most of them pneumothorax. Half of the patients subjected to sonographic biopsy showed peripheral pulmonary lesions, the other half tumours of the pleura, pleura and lung, mediastinum and chest wall. In 92% a positive result was obtained, whereas pneumothorax occurred in 2%. Leaving aside the intrapulmonary lesions, which would not have been visible by ultrasound, diagnosis with CT could be achieved in only 56% of the cases. CONCLUSION: In diagnosis of pleural, peripheral pulmonary and chest wall lesions, ultrasound guided biopsy is a safe, cost-effective, convenient and accurate method without exposure to x-rays.

[Parents as partners in school-based health promotion and addiction prevention: an empirical study for the example of Class2000]. / Eltern als Partner in der schulischen Gesundheitsförderung und Suchtvorbeugung: Eine empirische Studie am Beispiel Klasse2000.

Starting from the premise of the incomparable importance of the parent-child relationship for development, Class2000, a wide-reaching programme for the promotion of health and prevention of addiction in primary schools, focuses especially on the integration of parents. A questionnaire survey among 1430 parents in Hesse with children in the second primary class shows that the overriding majority of pupils (90 %) speak about Class2000 at home and initiate discussions with their parents on health-related topics. The various Class2000 information materials are acknowledged by up to 77 % of parents (comparatively more rarely in the case of the fathers) and are read, as a rule, with interest. Specific information on the contents of the programme is for the parents rather more important than general stimuli. Invitations to special informative events are accepted by well 80 % of the parents. Class2000 convinces more than 82 % of the participants. 71 % of the parents are prepared to contribute to the costs of Class2000. 12 % are undecided in this regard. Participation in parent evenings increases the readiness for financial involvement.

[Severe pulmonary hypertension in systemic lupus erythematosus. The successful therapy of an unusual manifestation]. / Schwere pulmonale Hypertonie bei systemischem Lupus erythematodes. Erfolgreiche Therapie bei einer ungewöhnlichen Manifestation.

UNLABELLED: OBJECTIVE AND CLINICAL FINDINGS: A 48-year-old woman was hospitalized because of haemoptysis. Until shortly before admission she had been on phenprocoumon after pulmonary embolism sustained 18 months previously. Six months before admission systemic lupus erythematodes (SLE) had been diagnosed and treatment with cortisone initiated. Physical examination revealed jugular venous congestion, tachycardia, dyspnoea on even minimal physical activity and pretibial oedema. INVESTIGATIONS: Lung scintigraphy showed a perfusion deficiency in the right lung, unchanged since a test 18 month before. Doppler echocardiography recorded an estimated pulmonary artery systolic pressure of 110 mm Hg. Angiography showed a fully patent superior vena cava and nearly complete occlusion of the main right pulmonary artery by a thrombus. DIAGNOSIS, TREATMENT AND COURSE: The haemoptyses ceased after 5 days of treatment with methylprednisolone, 130 mg daily for 5 days, reduced after 5 days to 80 mg i.v. every other day, plus cyclophosphamide, 50 mg daily by mouth. The pulmonary hypertension remained unchanged so that pulmonary thrombendarterectomy was indicated. Surgery revealed extensive mediastinal fibrosis and almost complete occlusion of the thick-walled right pulmonary artery by thrombus adherent to the wall. Histology showed vasculitis of the pulmonary arterial intima and of the small pulmonary vessels. After thrombectomy the pulmonary arterial systolic pressure fell to an remained at below 40 mm Hg. Phenprocoumon was continued (at an INR of 2.5-3.5) as was immunosuppressive treatment. The patient has remained free of symptoms and is able to be physically active. CONCLUSION: Pulmonary hypertension is a serious complication of SLE. Echocardiography is recommended for both the original diagnosis and serial follow-up, complemented by other imaging methods if indicated.

[Applications and uses of pleurography in patients with spontaneous pneumothorax]. / Anwendung und Nutzen der Pleurographie bei Patienten mit Spontanpneumothorax.

In a group of 74 patients, it proved possible by pleurography to localise bronchopleural fistulae, subpleural vesicles and interpleural adhesions. A comparison of the diagnostic procedures, pleurography, pulmonary CT scan and thoracoscopy, revealed that pleurography was best suited for the detection of bronchopleural fistulae, computed tomography was best in revealing subpleural or intrapulmonary vesicles, and thoracoscopy was best to demonstrate the presence of adhesions. In our patient material, the expanded diagnostic workup of spontaneous pneumothorax led to a substantial reduction in the so-called idiopathic pneumothorax from 53% to 26%. By preparing a differentiated therapeutic means, it was possible to appreciably reduce the recurrence rate of pneumothorax from 41% to 22%.

[Pleurodesis using an acrylate glue in the treatment of therapy-resistant symptomatic pneumothorax]. / Pleurodese mittels eines Acrylatklebers in der Behandlung therapieresistenter symptomatischer Pneumothoraces.

In 7 patients with therapy-resistant pneumothorax and a contraindication of surgery in obstructive large-bullae pulmonary emphysema, pulmonary fibrosis in the terminal stage (in one case bilateral), extensive pulmonary cysts, cystic pulmonary fibrosis, and large-cavernous pulmonary tuberculosis, an acrylate tissue adhesive was applied on 8 occasions through a pleural catheter. Following the rapid withdrawal of the catheter, the lungs remained fully expanded in five cases. In two cases, the tissue adhesive had to be applied interpleurally a second time, and in one case on three occasions at one-day intervals. In none of these cases did any major complications occur.

Concentrations of ampicillin and sulbactam in serum and in various compartments of the respiratory tract of patients.

After infusion of 2 g ampicillin and 1 g sulbactam the concentrations of these two beta-lactams were determined in serum and various compartments of the respiratory tract of 22 patients. About 30 min after the end of the infusion in 15 patients the mean serum concentration of ampicillin was 97 +/- 9.5 mg/l and of sulbactam 37.6 +/- 3.8 mg/l; in the biopsy samples of bronchial mucosa the concentration of ampicillin was 38.6 +/- 7.2 mg/kg and of sulbactam 28.1 +/- 5.2 mg/kg; in bronchial fluid the concentration of ampicillin was 0.6 +/- 0.1 mg/l and of sulbactam 0.3 +/- 0.1 mg/l (n = 15). In a further seven patients serum and pleural empyema samples were analysed and compared. The mean values of Cmax attained 1 to 2 h after the end of the infusion in pleural empyema were 7.6 +/- 3.1 mg/l and 6.2 +/- 1.6 mg/l for ampicillin and sulbactam, respectively. The two beta-lactams were eliminated markedly more slowly from empyema than from serum. These results show that ampicillin and sulbactam rapidly penetrate into various compartments of the respiratory tract and reach therapeutically active concentrations. The ratio of their concentrations (2:1) is largely the same as that in serum. The pharmacokinetic data therefore support the use of ampicillin/sulbactam in the perioperative prophylaxis and the treatment of bacterial infections of the lower respiratory tract.

Effect of prostaglandin E2 on eicosanoid release by human bronchial biopsy specimens from normal and inflamed mucosa.

BACKGROUND: Eicosanoids such as prostaglandin E2 (PGE2), thromboxane A2 (TXA2), and peptidoleukotrienes (pLT) are known to be biologically highly active lipid mediators, especially in human lung epithelium. PGE2 is thought to have mostly bronchoprotective effects, whereas pLT and TXA2 are bronchoconstrictive. This study was undertaken to assess the release and interaction of eicosanoids in human bronchial biopsy specimens of normal and inflamed mucosa. METHODS: Bronchial biopsy specimens were obtained from 16 patients, seven controls without signs of inflammation and nine patients with severe inflammatory processes in the epithelium. The release of pLT, TXA2 (measured as TXB2), and PGE2 was investigated using a "functional in vitro test" and the addition of several stimuli. RESULTS: Specimens incubated with arachidonic acid released higher amounts of pLT, TXB2, and PGE2 than unstimulated specimens. Preincubation with PGE2 revealed significant inhibition of arachidonic acid-induced release of pLT and TXB2 (> 50%). The inhibitory effect was higher in normal than in inflamed epithelium. CONCLUSIONS: Exogenous PGE2 has inhibitory effects on the release of pLT and TXB2 in human bronchial biopsy specimens. This finding could explain the bronchoprotective effect of inhaled PGE2 in normal subjects and asthmatic subjects as direct eicosanoid interactions. It also supports the concept of PGE2 as a bronchoprotective endogenous substance. The complex effects of PGE2 as a modulating mediator in inflammation may be worth investigating.

[Induction of direct antimicrobial activity through mammalian toll-like receptors]. / Induktion direkter antibakterieller Aktivität gegen Mycobacterium tuberculosis durch Toll-like-Rezeptoren.

Drosophila, the toll gene controls a powerful innate defense system against bacteria and fungi. Conserved through evolution, the mammalian innate immune system retains a family of homologous Toll-like receptors (TLRs) that are activated by microbial ligands to release cytokines that instruct the adaptive immune responses. Here we show that TLR2 activation leads to killing of intracellular Mycobacterium (M.) tuberculosis in both mouse and human macrophages. In mouse macrophages, bacterial lipoprotein activation of TLR2 leads to a nitric oxide-dependent killing of intracellular tubercle bacilli. In human monocytes and alveolar macrophages, bacterial lipoproteins similarly activated TLR2 to kill intracellular M. tuberculosis, however by an antimicrobial pathway that is nitric oxide independent. TLR2+CD14+CD68+ macrophages were detected in human lesions of tuberculous lymphadenitis within granulomas and surrounding foci of necrosis. These data provide evidence that mammalian TLRs have retained not only the structural features of Drosophila Toll that allow them to respond to microbial ligands, but also the ability directly to activate antimicrobial effector pathways at the site of infection.

[Development of a psychologically founded program for smoking cessation with adjuvant use of nicotine-containing chewing gum]. / Entwicklung eines psychologisch fundierten Raucherentwöhnungsprogrammes unter adjuvanter Anwendung von nikotinhaltigem Kaugummi.

This paper describes the development and testing of a quit-smoking programme employing the "clean-break" method and nicotine substitution. The first long-term results after 12 months show nicotine abstinence in 44.2% of all the participants, and thus confirm the therapeutic approach to quitting smoking.