[German guideline for diagnosis and management of idiopathic pulmonary fibrosis]. / S2K-Leitlinie zur Diagnostik und Therapie der idiopathischen Lungenfibrose.

Idiopathic pulmonary fibrosis is a fatal lung disease with a variable and unpredictable natural history and limited treatment options. Since publication of the ATS-ERS statement on IPF in the year 2000 diagnostic standards have improved and a considerable number of randomized controlled treatment trials have been published necessitating a revision. In the years 2006 - 2010 an international panel of IPF experts produced an evidence-based guideline on diagnosis and treatment of IPF, which was published in 2011. In order to implement this evidence-based guideline into the German Health System a group of German IPF experts translated and commented the international guideline, also including new publications in the field. A consensus conference was held in Bochum on December 3rd 2011 under the protectorate of the "Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin (DGP)" and supervised by the "Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften" (AWMF). Most recommendations of the international guideline were found to be appropriate for the german situation. Based on recent clinical studies "weak negative" treatment recommendations for pirfenidone and anticoagulation were changed into "weak positive" for pirfenidone and "strong negative" for anticoagulation. Based on negative results from the PANTHER-trial the recommendation for the combination therapy of prednisone plus azathiorpine plus N-acetlycsteine was also changed into strong negative für patients with definite IPF. This document summarizes essential parts of the international IPF guideline and the comments and recommendations of the German IPF consensus conference.

Culture and successful eradication of Helicobacter pylori from heterotopic gastric mucosa.

Helicobacter pylori colonizes the gastric mucosa of humans and can cause chronic gastritis, peptic ulcer disease, gastric cancer or mucosa-associated-lymphoid tissue (MALT) lymphoma. Here, we report the case of a 61-year-old male patient who presented with tickle of the throat, globus sensation and heartburn. In an esophagogastroduodenoscopy subpharyngeal localized heterotopic gastric mucosa (HGM), reflux esophagitis and a chronic gastritis were diagnosed. HGM and stomach were H. pylori positive as proven by culture and histopathological examination. After eradication therapy with a proton pump inhibitor (PPI), amoxicillin and clarithromycin followed by PPI treatment, the patient reported clinical improvement and the histopathological changes in the HGM due to H. pylori infection improved, too. This case report demonstrates that culture and susceptibility testing of H. pylori using established protocols succeeds not only from tissue samples of the stomach but also from heterotopic gastric mucosa. Eradication therapy may not only improve typical H. pylori associated discomforts of the stomach but also extragastric signs and symptoms of H. pylori infection.

[Case report of a rare occupational disease: a during life non-recognised occupational disease--talcosis]. / Fallbericht zu einer seltenen Berufskrankheit: Eine zu Lebzeiten nicht anerkannte Talkose.

Talc is a hydrated magnesium silicate used in the chemical, ceramic, cosmetic, leather, paper and building industries. Interstitial lung disease - talcosis - due to exclusive talc inhalation is a rare form of pneumoconiosis. More often, pulmonary disease due to talc is encountered after intravenous administration of talc during drug abuse. Talc can contain asbestos or quartz particles which induce asbestosis or silicosis. Here we present a case report about a worker who was exposed to talcum during his work in tire manufacturing. During his lifetime an occupational disease was not recognised. The deceased had been forwarded to cremation; the legally prescribed second inspection of the corpse induced the suspicion of an occupational disease and an autopsy was ordered. The autopsy revealed a lung fibrosis with honeycomb lung alterations and under polarised light a massive burden with birefringed crystalline particles could be visualised. Light and electron microscopic lung dust analyses could exclude an elevated asbestos lung burden. The element analysis of foreign body material in lung tissue confirmed its chemical composition of magnesium and silicon which was consistent with talc. Based on the pathological and mineralogical findings, the confirmed occupational exposure towards talc and, due to the exclusion of other possible causes (asbestos, quartz), the diagnose of a talc-induced interstitial lung fibrosis - talcosis - was established. This case emphasises the importance of pathological-anatomic examinations in combination with lung dust analysis to reveal occupational exposure as a cause of an interstitial lung disease.

Interplay of endothelial and inducible nitric oxide synthases modulates the vascular response to ischaemia-reperfusion in the rabbit lung.

AIM: Lung ischaemia-reperfusion induces nitric oxide synthesis and reactive nitrogen species, decreasing nitric oxide bioavailability. We hypothesized that in the ventilated lung, this process begins during ischaemia and intensifies with reperfusion, contributing to ischaemia-reperfusion-induced pulmonary vasoconstriction. The aim was to determine whether ischaemia-reperfusion alters inducible and endothelial nitric oxide synthase expression/activity, reactive nitrogen species generation, and nitric oxide bioavailability, potentially affecting pulmonary perfusion. METHODS: Ischaemia-reperfusion was induced for various times in anesthetized rabbits with ventilated lungs by reversibly occluding the right pulmonary artery and initiating reperfusion. Nitric oxide synthase activity/expression and phosphorylation, reactive nitrogen species generation and total nitrate/nitrite were determined in lung tissue. RESULTS: Inducible nitric oxide synthase expression and activity, and reactive nitrogen species formation coincided with increased pulmonary vascular resistance during reperfusion and increased with ischaemia duration, further increasing after 2-h reperfusion. Total nitrate/nitrite also increased with ischaemia but decreased after 2-h reperfusion. Pre-treatment with an inducible nitric oxide synthase inhibitor (1400W; Cayman Chemical Company, Ann Arbor, MI, USA) attenuated inducible nitric oxide synthase activity, reactive nitrogen species generation and pulmonary vascular resistance, but did not affect total nitrate/nitrite. Endothelial nitric oxide synthase expression was unchanged by ischaemia-reperfusion; however, its phosphorylation on serine 1177 and dephosphorylation on threonine 495 was uncoupled, suggesting decreased endothelial nitric oxide synthase activity. 1400W prevented uncoupling of endothelial nitric oxide synthase phosphorylation, maintaining its activity during reperfusion. CONCLUSION: Ischaemia-reperfusion up-regulates inducible nitric oxide synthesis and/activity, which coincides with reduced endothelial nitric oxide synthase activity as suggested by its uncoupling and may contribute to ischaemia-reperfusion-induced pulmonary vasoconstriction.

Nutritional strategies and growth in extremely low birth weight infants with bronchopulmonary dysplasia over the past 10 years.

OBJECTIVE: Changes in nutritional strategies over the past decade have been shown to improve postnatal growth in extremely low birth weight (ELBW) infants. We showed 10 years ago that the majority of these ELBW infants with bronchopulmonary dysplasia (BPD) suffer postnatal growth failure. We theorized that recent changes in nutritional support strategies would positively affect growth outcomes in ELBW infants with BPD. STUDY DESIGN: A retrospective study of 88 ELBW infants with BPD. Nutritional data, postnatal growth and BPD severity were compared across three cohorts: (1) weight gain ≤14 g kg(-1) per day, (2) 14.1 to 16 g kg(-1) per day and (3) ≥16 g kg(-1) per day from return to birth weight through discharge. We also compared these to a historical cohort. RESULT: In all, 73% of current subjects grew at or above fetal rates. There was less extrauterine growth restriction (EUGR) by weight and head circumference for those ELBW infants with BPD receiving higher amounts of protein. Aggressive early TPN and receipt of caloric-dense milk seemed to be the 'new' nutritional strategies improving growth for current ELBW infants with BPD compared with those 10 years ago. CONCLUSION: Despite a diagnosis of BPD, improved nutritional strategies have enhanced postnatal growth in infants at high risk for EUGR.

["Walking pneumonia" in primary sarcoma of the pulmonary artery]. / Wanderpneumonie bei primärem Sarkom der Pulmonalarterie.

A 74-year-old man suffered from symptoms of a left upper lobe pneumonia. Additional retrosternal masses were proved. Progression in the left upper lobe occurred in spite of antibiotic therapy; infiltrations of the right lower lobe were seen. No germs could be identified. Bronchoscopy and mediastinoscopy showed no pathological findings. His general health became worse, and the patient died under the clinical diagnosis of "wandering pneumonia" with finally suspicion of fulminant pulmonary artery embolism. Autopsy findings revealed an advanced stage of pulmonary artery sarcoma with myocardial infiltration and metastases in both kidneys and thyroid gland. General manifestation of pulmonary artery sarcoma usually are symptoms similar to those caused by pulmonary artery embolism with obstruction of pulmonary arterial flow. The unusual constellation of clinical findings similar to colliquating pneumonia results in secondary infection due to tumorous pulmonary infarction. The difficulties in diagnosis by biopsy are caused by primary intravascular growth of the neoplasms. Therefore early diagnosis in an operable tumor stage by means of CT, MR, and angiography is very important.

[Bleomycin-induced pulmonary fibrosis following chemotherapy of ovarian granulosa cell tumor]. / Bleomycininduzierte Lungenfibrose nach chemotherapeutisch behandeltem Granulosazelltumor des Ovars.

Bleomycin is used in the cytostatic therapeutical management of a variety of malignant tumours. The development of an interstitially accentuated pulmonary disease is a dreaded complication; this side effect may occur dose-related or not dose-related. We report on a 52-year old female patient with recurrent tumour after adnexectomy because of granulosa cell tumour, surgical re-intervention and subsequent polychemotherapy with cisplatin, etoposid and bleomycin (PEB regimen). Following this, the patient developed rapidly progressing lung fibrosis. There was no improvement in spite of combined high dose antibiotic and corticosteroid therapy. The patient finally died of respiratory insufficiency. Upon autopsy, apart from a circumscribed loco-regional tumour recurrence the clinical diagnosis of well advanced interstitial lung fibrosis presenting as so-called cytostatic pneumopathy was found. Immunohistochemical investigations using so-called proliferation markers revealed a markedly increased, centrifugally accentuated proliferative activity of both mesenchymal cells and of atypical pneumocyte regenerates, originating in areas of advanced parenchymal transformation and proceeding towards areas of supposedly intact lung tissue, a finding seen as an impressive histomorphological correlate of the clinically observed rapid progression of the disease. The development of a so-called bleomycin lung ist demonstrated from the formal pathogenetical point of view and correlated with the clinical course. The comparatively rapid shift of an expression of mediator systems with inflammatory properties towards local pulmonary or mesenchymal cells must be interpreted as the reason for the course of the disease, which in later phases could no longer be influenced by anti-inflammatory medication. These findings underline impressively the importance of early detection of developing pulmonary complications following cytostatic therapy. Apart from imaging techniques such as chest x-rays and HRCT, monitoring by 99mTc-DPTA inhalation is a very promising method for early demonstration of pulmonary alterations caused by cytostatically acting medication. This method registers precisely disturbances in pulmonary membrane permeability by measuring the radio nucleotide absorption rate along the alveolar-capillary membrane. In a therapeutical approach, next to the standard procedure of high-dose administration of corticosteroids, the influence of non-steroidal antiphlogistics and antioxidants is analysed, the growing knowledge on the cellular and molecular level possible leading to future therapeutical strategies, although the complex interactive mechanisms are still not completely understood.

[Pathology of rheumatoid lung]. / Pathologie der Rheumalunge.

In the framework of rheumatic illnesses, the lungs and pleura are often observed to be involved. Dependent on the basic illness in question, conditions of the bronchoalveolar system, vessels, lymphatic system, and pleura that have developed differently inter- and intra-individually can be diagnosed in topo-regionally variable forms and combinations. In the causal pathogenesis, the initial (auto-) immunological alteration of the alveolar septa plays a role. When the monocytes, macrophages, and fibroblasts are activated, as a result of a chronic inflammatory process there is increasing reparative proliferation, which finally leads to the non-specific end stage of irreversible interstitial fibrosis. The incidence and manifestation forms of lung changes show certain differences dependent on the underlying illness (e.g., rheumatoid arthritis, systemic lupus erythematosus, progressive systemic scleroderma, dermatomyositis and polymyositis, Sjögren syndrome, and mixed connective tissue disease). In addition to vasculitis and granulomatosis of the lung, therapy-induced lung changes must also be considered in the differential diagnosis since almost all basic therapeutic agents can cause this type of lung condition. Good knowledge of the parameters from the viewpoint of possible therapeutic measures is indispensable, as is close cooperation between the treating physician and the pathologist.

[Placentoid malformation of the lung]. / Plazentoide Malformation der Lunge.

The differential diagnosis of bullous and cystiform lung alterations comprises a relatively calculable number of various diseases, in which the most important are rare cystic tumors and congenial malformations, such as adenomatoid cystic malformation. We report on a rare clinical picture. In this case, the clinical diagnosis of localized unilateral emphysema caused by local displacement and with subsequent complications had led to "bullectomies" and pneumonectomy. Macroscopically, spongiform solid areas in association with areas of physaliform transformation were seen, corresponding histomorphologically to villous, placentalike formations. The "villous stroma" revealed focally regressive alterations, fatty islets and leiomyomatous areas. So far, the pathogenesis of this lesion, described as "placentoid malformation" due to its pathognomonic histological appearance, remains unclear. In contradiction to the much discussed hypothesis that this lesion may develop from pre-existing lung emphysema, our results suggest that this may be an independent lesion, possibly congenital hamartous malformation with self-developing progression. The clinically predominant emphysematic alterations are considered to be caused by a valve mechanism due to unphysiological traction forces, the lymphatic pathways regularly found in the border areas towards the original lung tissue, possibly playing an important etiological part.

[Proliferation kinetics of bronchioloalveolar tumorlets]. / Proliferationskinetik bronchiolo-alveolärer Tumorlets.

Bronchiolo-alveolar tumorlets--mostly clinically asymptomatic--generally are noticed as "contingent findings" in the diagnoses of interstitial fibrosing lung diseases. The growth fraction of these epithelial proliferates in the WHO classification summarized in the group of tumor like lesions was explored by immunohistochemical stainings with the PCNA and Ki67 (MIB1) antibodies and correlated with (pre-) neoplastic lesions of the lung. The proliferation indices varied between 0.029 to 0.67 (MIB1) and 0.057 to 0.81 (PCNA). Depending on the main disease the observation of cuboid metaplasias, areas of bronchiolization via tumorlets in inactive interstitial lung fibrosis up to bronchiolo alveolar tumorlets following interstitial lung disease after cytostatic treatment showed increasing proliferation indices. Accordingly to prencoplastic changes of the bronchial epithelium the findings suggest that interpretation of bronchiolo alveolar tumorlets as basic cells of malignant peripheral lung tumors seems to be possible. The value of these findings in relationship to the associated interstitial lung disease is discussed in the context of reflections related to the formal pathogenesis of so called scar cancer.

[Placentoid malformation of the lung as differential diagnosis of localized emphysema]. / Plazentoide Malformation der Lunge als Differentialdiagnose eines lokalisierten Emphysems.

In a 50-year old patient with a long history of chronic obstructive airway disease and pulmonary emphysema, unusual solid spongious areas adjacent to bullous tissue were detected by bullectomia because of mediastinal displacement and dyspnoea on exertion. Pathological anatomical diagnosis showed villous framework in the marginal regions of bullous transformed parenchyma. According to pathognomonic histological finding the lesion is known as placentoid malformation or placentoid bullous transmogrification, respectively. This disease must be differentiated against rare cystic tumours such as alveolar adenoma or sclerosing haemangioma as well as congenital lesions e.g. adenomatoid cystic malformation. The lesion presented here includes hamartomatous features, such as the presence of leiomyomatoid proliferations of smooth muscle cells and fatty tissue embedded in the villous stroma. The clinically predominant emphysematous transformation of the adjacent lung tissue is pathogenetically the result of a valve formation in combination with unphysiological traction forces. The ectatic lymphatic vessels in peripheral tissue may perhaps be of etiological importance. According to former studies this may be an congenital malformation with progressive development. Resection of affected lung parenchyma seems to be curative: so far, no recurrences have been noticed.

[Bronchiolitis obliterans after mycoplasma pneumonia]. / Bronchiolitis obliterans nach Mykoplasmenpneumonie.

Mycoplasmal pneumonias belong to the class of atypical pneumonias. Generally, the histomorphological findings are non-specific; occasionally there are fibrotic pulmonary changes in consequence of partial recovery. In the case under report we present a 27-year old male patient who developed an almost total atelectasis of the right lung subsequent to an unspecific respiratory infection. Serologically his findings were characterised by an extremely elevated mycoplasmal titre so that we had to assume he was suffering from mycoplasmal pneumonia taking an unusual course. Since it was not possible to restitute the lung despite intensive therapeutic efforts, right-sided pneumonectomy had to be performed. Histological examination of the resectate resulted in diagnosing a bronchiolitis obliterans with partially complete obliteration of the bronchi down to subsegmental size. The case presented here must therefore be interpreted as a rare course of mycoplasmal pneumonia associated with the development of a massive atelectasis on an underlying bronchiolitis obliterans.

[Local effects and changes in wound drainage in the free peritoneal cavity]. / Lokale Auswirkungen und Veränderungen von Wunddrainagen in der freien Bauchhöhle.

In a prospective randomised study 30 mongrel rabbits received two standard colon-resections. Three types of drains were tested: (latex-rubber-) Penrose-drains, rubbertube- and silicontube-drains, which were placed in the lower abdomen. As a closed drainage-system the extraperitoneal tip of the drain was placed in a closed subcutis-pocket. One of the two colon-anastomoses also was drained. The findings were recorded on the 7th postoperative day. A single mechanic alteration was found, an ulcer caused by a silicon-drain, that pushed against the abdominal wall. The other signs of mechanic irritation were microscopically unspecified inflammatory reactions to the foreign body drain. There was no ascending infection caused by the drain. All infections came from complications of the colon resections. In contrast to common opinions the drains in the lower abdomen showed no adhesions to the abdominal wall or organs. Only the entrance of the drain into the peritoneum and the cotton-gaze of Penrose-drains showed in nearly all cases adhesions. The large amount of adhesions to the anastomosis-drains came from complications of the colon-anastomoses. As a cause of material, rubber- and latex-rubber-drains showed large fibrin-clots on their surfaces. 7 days after the operation only about 20% of the drains had sufficient function. The rest was occluded by fibrin-clots in the lumen of the drain or the cotton-gaze. Over all there is no difference in changes and effects of the three different types of drains, but silicon as material showed advantages.

[Cerebral and basilar artery thrombosis following cervical spinal injury]. / Thrombose der Vertebral- und Basilararterie nach Verletzung der Halswirbelsäule.

Vertebral artery injury may complicate cervical spine injury and may result in severe neurological impairment. We present a case of a 54 year-old male who sustained a hyperextension injury of the neck during horse-back riding with cervical spine dislocation of C3/4. As a consequence of right-sided traumatic vertebral artery thrombosis and extension of the thrombus into the basilar artery the patient developed a brainstem and bilateral cerebellar infarction with fatal outcome. In a review of the literature the characteristics of 33 cases with vertebral artery injuries following cervical spine trauma and with associated neurological complications are described. The problems of vertebral artery injury are discussed concerning diagnosis and therapy.