[Transfusion-related acute lung injury (TRALI)]. / Transfusionsassoziierte akute Lungeninsuffizienz (TRALI).

Transfusion-related acute lung injury (TRALI) is primarily caused by transfusion of fresh frozen plasma or platelet concentrates and occurs by definition within 6 hours after transfusion with acute shortness of breath, hypoxemia and radiographically detectable bilateral infiltrates of the lung. Mostly leucocyte antibodies in the plasma of the blood donor (immunogenic TRALI) are responsible. Apart from antibodies, other substances such as biologically active lipids, mainly arising from the storage of platelet and red blood cell concentrates, can activate neutrophilic granulocytes and trigger a non-immunogenic TRALI. Pathophysiologically, granulocytes in the capillaries of the lung vessels release oxygen radicals and enzymes which damage the endothelial cells and cause pulmonary edema. Therapeutically, nasal oxygen administration may be sufficient. In severe cases, mechanical ventilation, invasive hemodynamic monitoring and fluid intake are required. Diuretics should be avoided. The administration of glucocorticoids is controversial. Antibody-related TRALI reactions occurred mainly after transfusion of fresh frozen plasma, which had been obtained from womenimmunized during pregnancy against leukocyte antigens. Therefore, in Germany, since 2009 only plasma from female donors without a history of prior or current pregnancy or negative testing for antibodies against HLA I, II or HNA has been used with the result that since then no TRALI-related death has been registered.

Docetaxel/gemcitabine or cisplatin/gemcitabine followed by docetaxel in the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC): results of a multicentre randomized phase II trial.

BACKGROUND: Most patients (pts) with metastatic non-small cell lung cancer (NSCLC) receive either single agents or chemotherapy doublets. Recent studies have demonstrated that triple-agent therapies may improve the response rate, but are associated with significant toxicity, and frequently do not prolong survival. A sequential triple-agent schedule may combine acceptable tolerability and good efficacy. We therefore conducted a multicentre, prospectively randomized study that evaluates a sequential three-drug schedule and a platinum-free doublet regimen. PATIENTS AND METHODS: The pts with union international contre le cancer (UICC) stage IV NSCLC were randomized to one of two schedules: in arm Doc-Gem, they received gemcitabine (900 mg/m(2), 30 min infusion) on days 1 and 8, and docetaxel (75 mg/m(2), 1 h infusion) on day 1, repeated every 3 weeks up to six cycles. In arm Cis-Gem-->Doc, gemcitabine (900 mg/m(2), days 1 and 8) and cisplatin (70 mg/m(2), 1 h infusion, day 1) were given for three cycles, followed by three cycles of docetaxel (100 mg/m(2), day 1, repeated every 3 weeks). RESULTS: One hundred and thirteen pts were randomized to arms Doc-Gem (55 pts) and Cis-Gem-->Doc (58 pts). With Doc-Gem, 20.4% of pts responded to the treatment whereas 31.0% responded in arm Cis-Gem-->Doc (overall response, intent-to-treat, difference not significant). The median time to progression was 3.6 months in arm Doc-Gem [95% confidence interval (CI) 1.4, 5.9] and 5.2 months in arm Cis-Gem-->Doc (95% CI 3.1, 7.3). The median survival was 8.7 months with treatment Doc-Gem (95% CI 5.7, 11.6) and 9.4 months with treatment Cis-Gem-->Doc (95% CI 7.8, 11.0). The 1-year survival rates were 34 and 35%, respectively. Mild to moderate leukopenia was frequently seen with both schedules. Other common adverse events (AE) were nausea/vomiting, thrombocytopenia, anaemia, diarrhoea, and infections. No significant differences in AEs were observed between the schedules except for nausea/vomiting, which occurred more frequently with Cis-Gem-->Doc. CONCLUSION: The sequential therapy comprising cisplatin, gemcitabine, and docetaxel demonstrated promising tumour control whereas the platinum-free combination (docetaxel/gemcitabine) was very well tolerated. However, the schedules resulted in comparable survival to recent large trials in pts with advanced NSCLC. The present results do not justify further phase III investigation.

Alpha-receptor restriction of coronary blood flow during atrial fibrillation.

The effects of atrial fibrillation (AF) on coronary circulation before and after alpha-receptor blockade were studied in 14 anesthetized, open-chest dogs. AF was induced by electrical stimulation of the left atrial appendage; identical rhythmic heart rates were adjusted by left atrial pacing. During atrial pacing, coronary vascular resistance (CVR) was 0.97 +/- 0.10 mm Hg X min X 100 g/ml (resistance units [RU]), coronary blood flow (CBF) 125 +/- 14 ml/min X 100 g, and oxygen saturation 30 +/- 2%; plasma epinephrine was 193 +/- 42 pg/ml and norepinephrine 584 +/- 111 pg/ml. During AF, CVR was higher (1.16 +/- 0.11 RU, p less than 0.0005), whereas CBF (92 +/- 9 ml/min X 100 g, p less than 0.001) and coronary sinus oxygen saturation (24 +/- 2%, p less than 0.0025) were lower than during atrial pacing. When AF was induced, epinephrine increased to 333 +/- 98 pg/ml (p less than 0.05) and norepinephrine to 1,005 +/- 214 pg/ml (p less than 0.005). The large increase in plasma catecholamines suggested an activation of the sympathoadrenal system during AF. In addition, the alpha-receptor blocker phenoxybenzamine (10 mg/kg, intravenously) abolished the differences in CVR, CBF and oxygen saturation between AF and atrial pacing. The data suggest that the decrease in CBF and increase in CVR during experimentally induced AF are caused by coronary vasoconstriction, mediated by sympathetic activation of alpha receptors in the coronary vascular bed.

Pleural penetration of ciprofloxacin in patients with empyema thoracis.

We evaluated the pharmacokinetics of a single 200-mg dose of ciprofloxacin, administered as a 30-minute infusion, into pleural exudate in five elderly patients with empyema thoracis. Ciprofloxacin was measured by HPLC and the pharmacokinetic parameters were determined by noncompartmental methods. Mean peak serum levels 30 minutes after administration were 1.98 +/- 0.07 mg/L. Terminal serum half-lives ranged from 3.9 to 5.1 h. Mean concentrations of ciprofloxacin in pleural exudate were 1.44 +/- 0.42 mg/L at a mean time of 4.5 +/- 2.5 h. After this time, the pleural exudate level exceeded the corresponding serum twofold to tenfold. The mean percentage penetration into the inflammatory compartment was approximately 210 percent. Our data suggested that ciprofloxacin penetrates well into the pleural fluid of patients with empyema thoracis. The concentrations achieved were well above the MIC90 of most pathogens normally found in patients with empyema thoracis for a period of approximately 12 h.

Juxtaglomerular angiotensin II formation.

Previous studies have indicated the existence of an unknown AII-forming enzyme (AFE) in the glomerular region. This investigation was undertaken to characterize this enzyme further and to elucidate its possible physiologic role. AFE activity was found in cortical tissue and in microdissected superficial and juxtamedullary glomeruli but not in renal medulla. It could be blocked by the converting enzyme (CE) inhibitors SQ 20881 (133.5 micrograms/ml; 70%), SQ 14225 (20 ng/ml; 80%), and DFP (20 micrograms/ml; 80%). In contrast to AI CE, AFE was neither blocked by EDTA nor stimulated by sodium chloride. In a further study, AFE activity and AII immunoreactivity were measured simultaneously in different renal structures and in plasma under control conditions and following water deprivation. Highest AII immunoreactivity was demonstrated in microdissected glomeruli (about 10 ng/g; N = 11) and lower amounts in cortical tissue (2.83 +/- 0.72 ng/g; N = 12), avascular cortical tissue (1.80 +/- 1.08 ng/g; N = 3), outer medulla (1.52 +/- 0.33 ng/g; N = 12), inner medulla (0.72 +/- 0.17 ng/g; N = 2), and in plasma (0.212 +/- 0.066 ng/ml; N = 12). Water deprivation had no measurable effect on AFE activity; but AII immunoreactivity increased significantly in all samples. This indicates that, in spite of the extremely high juxtaglomerular renin activity, AFE cannot be regarded as the limiting enzyme for local AII formation under the conditions investigated.

Kininase II in bronchoalveolar lavage fluid and serum of patients with pulmonary disorders.

In 68 patients with pulmonary diseases such as lung cancer (n = 32), sarcoidosis (n = 21) and chronic bronchitis (n = 15), kininase II (EC 3.4.15.1) (KII) was fluorimetrically (F-LKII) and the albumin concentration (LALB) spectrophotometrically measured in native unconcentrated bronchoalveolar lavage fluid. For comparison in serum, the KII was also spectrophotometrically (SP-SKII) and fluorimetrically (F-SKII) determined. In all patients, the mean (means) +/- SD F-LKII activity was 0.2 +/- 0.4 U/L, the LALB concentrations 0.17 +/- 0.44 g/L, and the resulting specific F-LKII activity was 3 +/- 3 U/g LALB. The highest elevations of LALB concentrations were determined in lung cancer. The highest activities of F-LKII, F-SKII, and SP-SKII were observed in sarcoidosis. A significant linear relation was found between F-LKII and LALB (R = 0.60, P less than 0.0002) and also between F-SKII and SP-SKII (R = 0.88, P less than 0.0001), but no relation could be established between F-SKII and F-LKII, indicating that the KII measured in lavage was not identical with the KII found in serum.

Alterations of carboxypeptidases N activities in patients with thyroid dysfunction.

Serum carboxypeptidases N (EC. 3.4.17.3) were determined spectrophotometrically in 87 patients with disturbances of thyroid function and in 131 euthyroid individuals, including 33 women taking estrogens for contraception. Carboxypeptidases N (CN) can be subdivided into CN1 and CN2, according to variable substrate affinity. In addition, measurements of blood pressure and in vitro tests of thyroid function were performed. In euthyroid controls, CN1 was negatively correlated with age. No significant differences between CN1 and CN2 have been observed with regard to sex. In patients with hyperthyroidism, the mean values of both enzymes were elevated, but this tendency proved to be significant only for CN2. In hypothyroid patients CN1 and CN2 levels were normal. Elevations of CN1 and CN2 in the hyperthyroid state seem not to be related to underlying immunological processes but to the thyroid hormone excess itself. In euthyroid women taking estrogens for contraception CN2 was also elevated.

PIP: The serum enzymes called carboxypeptidase N that split arginine or lysine from certain peptides, here termed CN1 and CN2, were determined in patients with thyroid disorders and in women taking oral contraceptives. The assays were done spectrophotometrically using synthetic hippuryl-substrates. The normal ranges in euthyroid subjects were 13-49 Units/1 for CN1 and 71-181 for CN2. In normal subjects, CN1 was inversely correlated with age. In hyperthyroid patients, the levels of both enzymes were elevated, significant only for CN2. Mean CN2 was significantly elevated in 33 women taking oral contraceptives, compared to euthyroid controls, 148.6 u/1, but was not outside the normal range.

Alterations of serum carboxypeptidases N and angiotensin-I-converting enzyme in malignant diseases.

The activities of serum carboxypeptidases N (E.C. 3.4.17.3) and serum angiotensin-I-converting enzyme (E.C. 3.4.15.1) were spectrophotometrically measured in patients with hematological disorders and in histologically proven bronchogenic carcinomas. The enzyme activities have been compared with various laboratory parameters. Controls were healthy subjects. No significant sex differences of carboxypeptidases N and angiotensin-I-converting enzyme were found in the healthy controls or in the whole patients' group. The carboxypeptidases N were significantly elevated in patients with lung cancer (p less than 0.0001) compared to the healthy controls. The angiotensin-I-converting enzyme was significantly reduced (p less than 0.0001) in serum of patients with bronchogenic carcinoma. In responders to chemo- and/or radiotherapy, the carboxypeptidases decreased and the angiotensin-I-converting enzyme increased to normal enzyme values. In non-responders to these therapies no change in these enzymes could be observed.

Comparison of two budesonide powder inhalers, Easyhaler and Turbuhaler, in steroid-naïve asthmatic patients.

The objective of this multicenter study was to compare the clinical efficacy, safety, and acceptability of Easyhaler and Turbuhaler for the delivery of budesonide 200 micrograms/dose twice daily in steroid-naïve asthmatic patients. Three hundred and twenty-six newly diagnosed, steroid-naïve adult patients with mild-to-moderate asthma were recruited into this randomized, double-blind, double-dummy, parallel-group study, comprising a 2-week run-in period and 8 weeks of treatment. Patients received budesonide inhalation powder 400 micrograms/day either via Easyhaler (n = 159) or via Turbuhaler (n = 167), plus salbutamol inhalation powder (100 micrograms/dose) via Easyhaler as rescue therapy. The study was completed by 292 patients: 143 in the Easyhaler group and 149 in the Turbuhaler group. The primary outcome variable, mean morning peak expiratory flow (PEF), improved significantly and almost similarly by 36.3 and 30.6 l/min, respectively, from run-in to weeks 7-8. At weeks 7-8, the mean (SE) difference in morning PEF between the two treatments was 7.1 (9.4) l/min (90% CI from -8.4 to 22.6) on per protocol analysis, which was within the defined limits for therapeutic equivalence. There were no significant differences between treatments in terms of secondary efficacy variables or adverse events. However, patients found Easyhaler more acceptable than Turbuhaler. The results show that budesonide via Easyhaler is clinically as effective as Pulmicort Turbuhaler when equal daily doses of budesonide are delivered to steroid-naïve asthmatic patients. Moreover, patients found Easyhaler more acceptable than Turbuhaler, and a majority would prefer Easyhaler if given a choice.

Kininase I and II activities in serum of patients with lung diseases.

In serum of 530 patients with various lung diseases and in 70 healthy control subjects, kininase I (E.C. 3.4.17.3) and kininase II (E.C. 3.4.15.1) were measured spectrophotometrically using hippuryl-L-arginine for estimation of kininase Ia (KIa), hippuryl-L-lysine for kininase Ib (KIb) and hippuryl-L-histidyl-L-leucine for kininase II (KII). KIa and KIb were significantly elevated (p less than 0.02) in lung cancer and sarcoidosis, compared to tuberculosis and healthy controls. There was an increase (p less than 0.05) in lung cancer in relation to sarcoidosis, chronic obstructive bronchitis, tuberculosis, pulmonary fibrosis and healthy control subjects. KII was significantly elevated in sarcoidosis (p less than 0.0001). According to the histological types of lung cancer, no differences of KIa, KIb and KII have been found. The ratio KIa/KIb X KII was 2.3 in lung cancer and 6.7 in the group with sarcoidosis. These results show that the determination of kininases can be used for diagnosis of lung diseases.

Value of determination of kininase II in bronchoalveolar lavage fluid.

Kininase II (KII), identical with angiotensin-I-converting enzyme (E.C. 3.4.15.1) was characterized biochemically and assayed fluorimetrically in bronchoalveolar lavage fluid and serum of 153 patients with several pulmonary disorders. The albumin concentrations of serum and bronchoalveolar lavage fluid (BLF) have also been measured. The pH optimum of KII derived from BLF (LKII) was 8.0. The Michaelis Menten constant was 38.5 mumol/l using benzyloxycarbonyl-phenylalanyl-histidyl-leucine as synthetic substrate. LKII could be inhibited between 80 and 100% by EDTA, phenanthroline, dimercapto-1-propane-sulfonic acid (DMPS), hydroxyquinoline and captopril. The LKII activity (mU/ml BLF) showed no differences in all lung diseases, but the specific LKII (mU/mg albumin) was significantly elevated in sarcoidosis compared to pneumonia (p less than 0.05), fibrosis (p less than 0.05), chronic obstructive bronchitis (p less than 0.005) and lung cancer (p less than 0.01), but not in tuberculosis. This study shows that LKII is measurable in native, unconcentrated BLF and the results indicate that LKII could be useful for diagnosis of pulmonary disorders.

Cost saving with ultrasonography in a developing country district hospital.

OBJECTIVE: To estimate the potential monetary reduction induced by the introduction of an ultrasound unit in a major district hospital in a developing country. DESIGN: Propective study. SUBJECTS: Patients referred with abnominal diseases and pregnancy. SETTING: Wad Medani Teaching Hospital, Central Sudan. RESULTS: Local specialists referring the patients stated that an estimated 792 radiologic procedures would have been carried out to obtain the same amount of information as achieved by ultrasound. Such procedures budgeted approximately 8100 US dollars, in terms of equipment, material and personnel by 1987 rates. Such savings have benefited all departments of the hospital. CONCLUSION: The authors consider this as evidence for the fact that despite its initial high investment (15,000 US dollars), availability of ultrasound virtually reduced expenditure on other radiological diagnostic procedures. This is of special benefit for the limited budgets of hospitals in non-industrialised countries.

Absence of the left pulmonary artery in a young man with haemoptysis.

We report the case of a white male aged 21 yrs, who was admitted for acute onset of haemoptysis. His past medical history was normal and he had not previously been hospitalized. He was very active in track and field sports and was trained in scuba-diving. Physical examination revealed a grade 2/6 holosystolic heart murmur. Laboratory parameters, blood gases and pulmonary function tests were within the normal range. Fibreoptic bronchoscopy revealed normal geometry of the bronchi, with blood clots in the left lower lobe. An X-ray of the chest showed that the heart was shifted to the left side. In the perfusion scan, defects of the tracer on the left lung were detected. By ergospirometry, no significantly pathological response to exercise using a bicycle ergometer could be observed. By means of pulmonary artery catheterization, cardioangiography and selective angiography of the aorta the absence of the left pulmonary artery could be established, without any further malformations of the cardiopulmonary system. Because of the spontaneous cessation of haemoptysis, no surgical intervention was necessary.

[Bronchoalveolar lavage in the assessment of lung diseases]. / Die bronchoalveoläre Lavage zur Beurteilung von Lungenerkrankungen.

The bronchoalveolar lavage (BAL) is a new method of low risk for the differential diagnosis of pulmonary disorders. In the BAL cells, microorganisms, and non-corpuscular components derived from the alveolar space can be investigated. The analysis of the recovered cells delivers information about the diseases. Lymphocyte predominant disorders are sarcoidosis, hypersensitivity pneumonitis, alveolitis, tuberculosis, lymphangiosis carcinomatosa and pneumoconiosis. The prognosis of sarcoidosis depends on the ratio of the T-helper and T-suppressor cells. Neutrophil predominant disorders are seen in idiopathic pulmonary fibrosis, asbestosis and collagen vascular disorders. BAL has also become an established approach to the diagnosis of infections in the immunosuppressed patients. Also tumor cells and tumor markers can be detected. Phagocytosed particles are an indication of inhaled dust. Asbestos fibres and silica are visible by light microscopy and metals are detected by x-ray energy dispersive spectrometry.

[Clinical studies of the incidence of pulmonary and extrapulmonary tuberculosis]. / Klinische Untersuchungen über die Häufigkeit der pulmonalen und extrapulmonalen Tuberkulose.

On the whole 797 patients (mean age 49.5 +/- 18.6 years) with tuberculosis who were hospitalized during 1987 and the first half of the year 1994 were investigated. 148 (18.6%) of these patients were foreigners. Regarding the age, the patients of German origin were mostly above 40 years (70.5%). Within the group of foreigners, 61.5% were below 40 years. 83.3% of the patients suffered from pulmonary and 11.4% from extrapulmonary and 11.4% from extrapulmonary tuberculosis. 5.3% of these patients had both manifestations. The tuberculin tine test was positive in 95.7% and negative in 4.3%. In 63.9% of all patients the tuberculosis was localized in the upper lobe of the lung. The tuberculosis was established bacteriologically in 56.0% and histologically in 16.5%. Both methods were applied in 13.6%. The tuberculosis was deteriorated by chronic alcoholism. Malignant diseases were recorded in 17 (2.1%) of the patients. 22 (2.8%) died during their stay at the hospital.

[Report by the Scientific Working Group for Therapy of Lung Diseases: German Fibrosis Register with initial results]. / Mitteilung der Wissenschaftlichen Arbeitsgemeinschaft für die Therapie von Lungenkrankheiten (WATL): Deutsches Fibroseregister mit ersten Ergebnissen.

The aim of this study was to evaluate the occurrence of interstitial lung diseases (ILD) in Germany. Therefore members of the WATL developed a questionnaire which was sent to pulmonary and other physicians who may encounter patients with ILD. In 1995 altogether 234 patients (105 males, 129 females, mean age 51 years, minimum 12, maximum 88 years) were referred to the registry. 126 of these patients were non-smoker, 58 ex-smoker, 45 smoker and in 5 patients no information was given. The following ILD were reported: sarcoidosis (n = 83, 36 males, 47 females), idiopathic pulmonary fibrosis (n = 76, 35 males, 41 females), idiopathic pulmonary fibrosis (n = 76, 35 males, 41 females), alveolitis (n = 31, 12 males, 19 females), bronchiolitis obliterans organizing pneumonia (n = 16, 6 males, 10 females) and others (n = 28, 16 males, 12 females). These preliminary data show that sarcoidosis (35%) and idiopathic fibrosis (33%) were the most frequently registered ILD.

Acute intoxication of a hydrazine-like gas by 19 workers in a garbage dump.

Nineteen workers (18 males, 1 female) of a garbage dump (mean age 39.9 years, range 19-58 years) were admitted to our hospital because of inhalation of a hydrazine-like gas of unknown origin. They complained of an ammoniacal odor with sweet taste followed by burning of the eyes, rawness in the throat and dyspnea, dizziness and nausea. Ten patients (group A) arrived about 2 h after they had experienced their first symptoms. The nine other patients (group B) were admitted about 70 h later. On the second day the white cell counts were significantly elevated compared to those of the days before and after (P < 0.02-0.005). The lung function showed in two patients a moderate obstruction. The PO2 was significantly reduced within 1 to 12 h after admission (P < 0.02-0.005) compared to the measurement before (P < 0.005) and after 25 (P < 0.02) and 50 (P < 0.01) h. A significantly reduced PCO2 was found after 25 h compared to the time of admission (P < 0.03). These investigations show that workers of a garbage dump had an alarming decrease of oxygen after inhalation of nitrogenous gases released by the trash.