[Effect of Inhalation of Tobramycin for 12 Months on Reduction of Hospitalisation Rate in Severe COPD]. / Inhalation von Tobramycin über 12 Monate zur Senkung der Hospitalisationsrate bei schwerer COPD mit gehäuften Hospitalisationen.

INTRODUCTION: Bacterial colonisation in stable disease of severe COPD and bronchiectasis can cause recurrent hospital treatment, which has a negative impact on the patient's prognosis. A multicentre study has investigated if daily inhalation of tobramycin for one year would lower the number of hospitalisations in severe COPD. METHODS: 44 patients with severe COPD [FEV1 % of predicted value: 42.8 ± 7,1 tobramycin group (T) and 33.5 ± 10.3 placebo group (P)] and a minimum of two hospitalisations in the year before inclusion were randomly assigned to inhale twice daily for 12 months 80 mg tobramycin or isotonic saline (placebo). Concomitant therapy was according to the GOLD guidelines. Primary end point was the number of hospitalisations in the period of study, secondary end points were pulmonary function test and 6 MWD. RESULTS: Inhalation of T changed the number of hospitalisations from 2.8 ± 0.5 per year to 3.5 ± 2.7, P from 3.0 ± 1,4 to 2.3 ± 2.2. These differences and the results for secondary endpoints did not reach significance. The dropout rate was high, only 6 patients (T) and 14 patients (P) finished the study per protocol. CONCLUSION: Inhalation with 160 mg tobramycin by means of a nebuliser over a 12-month period did not reduce the number of hospitalisations for patients with severe COPD and a minimum of two hospitalisations compared to placebo. The severity of the disease was the main reason for the high dropout rate.

A phase II study on safety and efficacy of high-dose N-acetylcysteine in patients with cystic fibrosis.

OBJECTIVE: We conducted a single-centre, randomised, double-blinded, placebo-controlled phase II clinical study to test safety and efficacy of a 12-week therapy with low-dose (700 mg/daily) or high-dose (2800 mg/daily) of NAC. METHODS: Twenty-one patients (DeltaF508 homo/heterozygous, FEV1>40% pred.) were included in the study. After a 3-weeks placebo run-in phase, 11 patients received low-dose NAC, and 10 patients received high-dose NAC. Outcomes included safety and clinical parameters, inflammatory (total leukocyte numbers, cell differentials, TNF-alpha, IL-8) measures in induced sputum, and concentrations of extracellular glutathione in induced sputum and blood. RESULTS: High-dose NAC was a well-tolerated and safe medication. High-dose NAC did not alter clinical or inflammatory parameters. However, extracellular glutathione in induced sputum tended to increase on high-dose NAC. CONCLUSIONS: High-dose NAC is a well-tolerated and safe medication for a prolonged therapy of patients with CF with a potential to increase extracellular glutathione in CF airways.

[The effects of physical training on the body composition of patients with COPD]. / Die Auswirkungen von Sport auf die Körperzusammensetzung von COPD-Patienten.

AIM: The following controlled trial was conducted to determine the positive effects of exercise on the body composition of patients suffering from COPD. METHODS: A group consisting of 23 COPD patients who regularly participated in a guided exercise programme was compared with a control group consisting of 19 COPD patients who did not exercise. The relative changes of body mass index (BMI), body cell mass in % [BCM-(%)], extra cellular mass/body cell mass index (ECM/BCM index) and phase angle (angle between sinus current and sinus voltage) after 6 months and after one year were analysed for statistical differences. The values of BMI, BCM-(%), ECM/BCM index and phase angle at the beginning of the study were compared with the results during the course of the 18 months training merely within the exercising group. The body composition of the patients was determined with the help of the bioelectric impedance analysis (BIA) using the system "Nutriguard M" produced by "Data Input". RESULTS: Significantly raised phase angle values as well as significantly increased BCM-(%) values and a decreased ECM/BCM index were found in the group of patients who exercised compared with the COPD patients who did not exercise. While there were no differences concerning the BMI value, significant increases in BCM-(%) and phase angle and a significant decrease of the ECM/BCM index could be detected within the group that had been exercising. The best values were recorded after 6 months of exercising. The differences of the group responses resulted from a worsening of the body composition in the control group rather than from improvements in the exercise group. CONCLUSION: Physical exercise can improve or at least stabilise the body composition of COPD patients and should be recommended.

[Improvement in expiratory peak flow (PEF) of COPD patients due to "lung" sport for 12 months]. / Verbesserung des exspiratorischen Spitzenflusses (PEF) von COPD-Patienten durch Lungensport über 12 Monate.

This prospective, randomised, controlled study deals with the question whether it is possible to induce an improvement of peak expiratory flow (PEF) in patients suffering from COPD by a structured "lung" sport programme over a longer period of time (12 months). Furthermore, a comparison with the spontaneous course of the disease was performed. A group of 7 COPD patients (1 man, 6 women, mean age 70 years, COPD grade II - III according to GOLD) who regularly took part in a structured lung sport programme was compared with a control group of 10 COPD patients (5 men, 5 women, mean age 67.5 years, COPD grade II - III according to GOLD) who denied doing sport. The PEF values of the patients were measured after 0 and 12 months during exacerbation-free intervals. The relative changes of PEF in percent after one year were statistically compared. There was an improvement of PEF of about + 10.4 % (standard deviation SD +/- 8.9 %) after 12 months of lung sport. The spontaneous course of the disease of the patients who denied doing sport led to a decrease of PEF of about - 8.8 % (standard deviation SD +/- 11.5 %). The difference in PEF changes with respect to "lung" sport and to the spontaneous course of COPD was highly significant (p < 0.01) in spite of a high standard deviation. The long lasting improvement of PEF due to sport among COPD patients speaks in favour of a positive effect of "lung" sport.

[Gastrointestinal tuberculosis as the main manifestation of systemic tuberculosis]. / Darmtuberkulose als Hauptmanifestation einer systemischen Tuberkulose.

We describe a rare case of tuberculosis with mainly gastrointestinal problems. The 52-year-aged female patient came to hospital with unclear pain in the lower abdomen and ascites that was refractory to therapy. The computed tomography of the thorax showed right-sided confluating lymphoid nodes, the CT of the abdomen showed ascites and nodular structures near the coecum. Tissue samples were taken from the mucosa of the colon, the inflammatory altered peritoneum, the left bronchus of the upper lobe and the confluating lymphoid nodes in the mediastinum during colonoscopy, diagnostic laparoscopy and bronchoscopy. The samples from the peritoneum showed granulomas with caseating necroses in histological slices. Mycobacterium tuberculosis was detected by PCR in the tissue samples from the lymphoid tissue of the mediastinum. Furthermore, Mycobacterium tuberculosis grew in cultures from samples of the abdominal ascites. The symptoms and pathological findings improved under a therapy comprising isoniazid, rifampicin, ethambutol and pyrazinamid.

[Retroperitoneal bronchogenic cyst]. / Retroperitoneale bronchogene Zyste.

We describe a 35-year-old female patient who underwent surgery because of a coincidentally occurring cryptic tumour near the left adrenal gland and a right renal carcinoma (pT1, N0, G2, R0). The left-sided tumour was intraoperatively identified as a cystic structure filled with secretion. Histopathological analysis provided the diagnosis of a bronchogenic cyst.

[Villous adenoma of the renal pelvis and ureter]. / Villöses Adenom des Nierenbeckens und Ureters.

Villous adenomas of the urinary tract are extremely rare tumours belonging to the adenoepithelial metaplasias. They can be associated with other neoplasias, especially with carcinomas. We describe the case of an 85-year-old female patient suffering from a villous adenoma of the renal pelvis and ureter.

[Alveolar proteinosis--therapy concept with a modified BAL]. / Alveolarproteinose--Therapieansatz mittels modifizierter BAL.

UNLABELLED: BACKGROUND/PATIENTS: This report is about two patients (male, 48 and 35 years old) with a primary alveolar proteinosis where the indication for therapeutic lavage was given. The standard is lavage with up to 50 litres fluid. METHODS: We preferred a modified therapy with the so called "ambu-lavage". With this kind of Lavage, first described by Kronenberger et al., one lung is filled with one litre warm (37 degrees C) NaCl-fluid. Then this fluid is mixed up with an ambu-bellows for three minutes and then the fluid is removed of the lung. More cycles with 500 ml fluid follow until the lung is lavaged with five litres. In summary every lung was lavaged two to three times. The protein concentration was checked in every lavage portion. RESULTS: Both patients tolerated these procedures well, in anaesthesia with a double-lumen-tube. There were no complications. The pulmonary function test and blood-gas-analysis could be improved significantly. Dyspnoea disappeared. CONCLUSION: This case-report shows two cases of alveolar-proteinosis which were treated well with the "ambu-lavage" which takes less time than the standard-lavage.

[Pneumonia induced by nocardia -- a case report]. / Nokardien-Pneumonie - eine Kasuistik.

We describe a case of lung manifestation of nocardiosis with upper lobe shrinking of the right lung in a 45 year old patient without evident signs of an immuno-compromising illness. The patient came to the hospital in a reduced general state of health with severe cough, red and brown sputum and exertional dyspnoea. X-ray pictures of the thorax showed inflammatory infiltration and shrinking of the upper left lobe of the right lung. Gram-positive, branching rods were detected in the patient's bronchial secretion with the microscope and in cultures. Nocoardia transvalensis was identified via polymerase chain reaction (PCR). The antibiotic therapy was planned according to the bacterial resistance pattern. Imipenem was administered for 5 weeks and Amikacin was added for 3 weeks in the 3 (rd) week of therapy. The patient left the hospital in a good general state of health. There was no relapse.

[Tuberculosis induced by Bacillus Calmette-Guerin immuno-prophylaxis -- case study]. / Durch Bacillus Calmette-Guerin induzierte Tuberkulose.

We describe a case of miliary tuberculosis induced by Bacillus Calmette-Guerin (BCG) as a complication of an infection after BCG-instillation therapy into the bladder because of bladder carcinoma. Bacilli surely entered blood circulation via an urethral lesion because of a difficult catheterisation. The 60 year old patient was administered to the hospital with septic temperature 4 four days after BCG instillation. CT showed a miliary patten and the diagnosis was confirmed by bronchoscopy: transbronchial biopsy showed granulomatous infiltration and an acid-fast rod-bacterium was detected in bronchial slime. Symptoms vanished after a consequent antituberculous triple therapy regime and the patient left hospital in a good general state of health.

Glutathione and glutathione peroxidase in sputum samples of adult patients with cystic fibrosis.

BACKGROUND: Reduced glutathione (GSH) is a major antioxidant in the lung. In cystic fibrosis (CF) patients, extracellular GSH levels of lower airways, obtained by bronchoalveolar lavage (BAL), were reported to be lower than non-CF individuals. METHODS: Upper airway secretions of stable adult CF patients (29 spontaneous and 13 induced sputum) and non-CF individuals (14 healthy and 12 asthmatics; all induced sputum) were analyzed for total glutathione (i.e. the sum of reduced, GSH, and oxidized, GSSG, forms), GSH and GSSG levels by enzymatic kinetic assay. RESULTS: In CF, both spontaneous and induced sputum samples were comparable in total glutathione levels which were surprisingly high (median concentration of 9.2 (range 1.4-65.2) and 11.6 (1.1-69.8) microM, respectively). In non-CF individuals, total glutathione levels were significantly lower (healthy 2.8 (1.0-12.3), asthmatics (5.3 (1.3-19.2) microM; p<0.001, both vs. CF). In CF, more than 90% of total glutathione was represented by GSH, whereas in non-CF controls, GSH made up less than 50% of total glutathione (p<0.001). CONCLUSIONS: In contrast to BAL, CF sputum contains high levels of GSH. Sputum induction is a potentially useful procedure to monitor antioxidant levels in upper airways of CF patients.

Prevalence of Aspergillus fumigatus and other fungal species in the sputum of adult patients with cystic fibrosis.

Aspergillus fumigatus is often found in the respiratory tract secretions of patients with cystic fibrosis (CF), although the role of the fungus for progression of pulmonary disease remains unclear. This study aimed to investigate the frequency of A. fumigatus and other fungi in sputum of adult CF patients using different methods for culture and microscopy. Results from the analysis of 369 samples from 94 patients showed that A. fumigatus could be isolated in 45.7% of patients. Other moulds were rare, but the yeast Candida albicans was another frequent isolate, detected in 75.5% of patients. A comparison of different culture media showed no difference between a selective medium developed to specifically inhibit Pseudomonas aeruginosa and a standard fungal culture medium for growth of A. fumigatus, although both were more efficient for detection of fungi than other bacterial culture media. Fluorescent microscopy with calcofluor white was more sensitive for detection of fungal hyphae in undiluted sputum than standard methylene blue staining. This study shows that A. fumigatus and C. albicans have a high frequency in adult CF patients. Microbiological analysis should routinely include methods for specific identification of fungi to monitor for potential complications arising from fungal disease in these patients.

[Malnutrition in COPD]. / Malnutrition bei COPD.

During the last years our knowledge about the malnutrition of patients with COPD has grown. Weight loss is a problem of some patients with COPD, but, as we know today by techniques of body composition measurement much more patients have reduced muscle mass. The reason for this is complex and involves many body systems. Nutritional intervention alone is not successful in many patients. We have to accept that COPD is a kind of systemic disease which does not only involve the lung. Thus, future therapies have to include not only treatment of the bronchial system.

[Anxiety: an aspect of the interaction of doctor and patients on the waiting-list and after lung-transplantation]. / Angst: Ein Aspekt der Interaktion von Arzt und Patient auf der Warteliste und nach Lungentransplantation.

Anxiety occurs frequently in patients who are on the waiting-list for a lung-transplantation or have already been transplanted. In this context anxiety is a theme of every interaction of doctor and patient but often remains unrecognized because it hides behind bodily symptoms and mechanisms of defense. Anxiety affects patients' behavior and compliance and may afflict - especially if not recognized - doctors' decisions and thus patients' health and survival. It is therefore necessary to recognize and to openly handle anxiety in the interaction of doctor and patient.

Diabetes mellitus in patients with cystic fibrosis: the impact of diabetes mellitus on pulmonary function and clinical outcome.

In this multicenter study, the impact of CF-related diabetes mellitus (CFRD) on pulmonary function and clinical outcome has been investigated. To better characterize the relationship between insulin deficiency and clinical outcome we prospectively followed a group of 56 CF patients, 28 with CFRD (group 1) and 28 without diabetes (group 2) for 5 years. The clinical course of the patients was registered at each center. Data included were mortality, pulmonary function, body mass index, in-patient treatment, and CF-typical and diabetes typical complications. At the end of the study nearly twice the number of patients had died in group 1 as compared to group 2, however due to the low patient number this did not reach statistical significance. In patients with diabetes FEV1 and FVC declined significantly over the five year study period, whereas patients without diabetes did not show a significant decline during the study period. Retinopathy, nephropathy, and neuropathy were only observed in diabetic patients. In conclusion, the data presented in this prospective, multicenter study give evidence that insulin deficiency leads to a direct decline in pulmonary function suggesting a cause and effect relationship between insulin deficiency and lung disease.

Expression of human beta-defensin-1 promotes differentiation of keratinocytes.

Epithelial cells have been shown to express the antibiotic peptides human beta-defensins-1 and 2. While beta-defensin-2 is known to be up-regulated by bacterial factors and proinflammatory mediators, the expression of beta-defensin-1 does not appear to be affected by these mediators. To determine the regulation and function of beta-defensin-1 we analyzed its expression upon stimulation of inflammatory mediators in vitro and ex vivo. In immortalized human cell lines (HaCaT) and nasal polyps beta-defensin-1 was not induced upon incubation with bacteria or proinflammatory mediators, suggesting that the inertness of beta-defensin-1 expression levels is not the result of the shortcoming of HaCaT cells. As proliferation and regeneration play an important role at sites of inflammation, we examined the expression level of beta-defensin-1 in relation to the differentiation and proliferation of HaCaT cells. beta-defensin-1 mRNA levels remained low during proliferation but were highly induced upon differentiation. In contrast, beta-defensin-2 expression was unaffected under these conditions. To examine the function of beta-defensin-1 in cellular proliferation and differentiation processes beta-defensin-1 was overexpressed in keratinocytes. Protein expression analysis of the differentiation marker keratin 10 revealed that its expression is highly induced in the presence of increased concentrations of beta-defensin-1. Hence our data indicate that high expression of beta-defensin-1 promotes cell differentiation processes of keratinocytes.

In situ NMR observation of mono- and binuclear rhodium dihydride complexes using parahydrogen-induced polarization.

Starting from the binuclear complex [RhCl(NBD)]2 (NBD = 2,5-norbornadiene) in the presence of the phosphines L = PMe3, PMe2Ph, PMePh2, PEt3, PEt2Ph, PEtPh2, or P(n-butyl)3, various mononuclear dihydrides of the type Rh(H)2CIL3, i.e., those of the homogeneous hydrogenation catalysts RhCIL3, have been obtained upon addition of parahydrogen, and their 1H NMR spectra have been investigated using parahydrogen-induced polarization (PHIP). Furthermore, the two binuclear complexes (H)(Cl)Rh(PMe3)2(mu-Cl)(mu-H)Rh(PMe3) and (H)(Cl)Rh(PMe2Ph)2(mu-Cl)(mu-H)Rh(PMe2Ph) have been detected and characterized by means of this in situ NMR method. Analogous complexes with trifluoroacetate instead of chloride, i.e., Rh(H)2(CF3COO)L3, have been generated in situ starting from Rh(NBD)(acac) in the presence of trifluoroacetic acid in combination with the phosphines L = PPh3, PEt2Ph, PEt3, and P(n-butyl)3, and their 1H NMR parameters have been determined.