[Hemoglobin drop after thrombolytic therapy in a 57-year-old stroke patient with "erosive gastritis"]. / Hämoglobinabfall nach einer Thrombolysetherapie bei einer 57-jährigen Patientin mit Schlaganfall und "erosiver Gastritis".

A 57-year-old woman underwent esophagogastroduodenoscopy due to a continuous drop in hemoglobin levels reaching 7.4 g/dl after treatment with intravenous thrombolytic therapy 1 week earlier because of an ischemic insult. Numerous erosive lesions were found in the gastric corpus. Histological staining of a specimen from the gastric lesions revealed a poorly differentiated adenocarcinoma. Immunohistochemical examination confirmed the diagnosis of gastric metastasis from lung cancer based on positive staining for thyroid transcriptional factor­1 (TTF-1) and cytokeratin 7 (CK7) as well as via negative staining for caudal-type homeobox­2 (CDX-2). Chest computed tomography demonstrated a mediastinal mass, measuring 3.2 cm and involving the cervical and supraclavicular lymph nodes. A lymph node was subsequently extirpated. Immunohistochemical examination confirmed the diagnosis of lymph node metastasis from lung cancer by positive staining for TTF­1 and CK7. Symptomatic gastric metastasis from lung cancer is an extremely rare clinical entity. Transesophageal echocardiography detected a mass measuring 1.6 cm at the mitral valve with pericardial effusion. On the basis of the echocardiographic findings, a malignant origin was suggested after exclusion of infectious endocarditis. We assumed that the multiple organ infarctions (spleen, kidney, and brain) and gastric hematogenous metastasis must have been caused by disseminated arterial tumor embolism from the intracardiac metastasis. The patient was treated palliatively and died.

[Recurrent bleeding of a duodenal ulcer in a 55-year-old man after heart transplantation]. / Rezidivierende Blutungen aus einem Ulcus duodeni bei einem 55-jährigen Patienten nach Herztransplantation.

Duodenal ulcers are most often caused by Helicobacter pylori (HP) infection, followed by nonsteroidal anti-inflammatory drugs and hypoperfusion. Posttransplant lymphoproliferative disorder (PTLD) occurs in about 1-6.3% of patients with a heart transplant under immunosuppression therapy. Up to 25% of cases of PTLD have gastrointestinal involvement. Due to a wide spectrum of clinical symptoms and pathological entities, the diagnosis can be challenging. We report the case of a 55-year-old man 12 years after receiving a heart transplant being treated with immunosuppressive agents (tacrolimus) who presented with recurrent bleeding from peptic duodeni. Immunohistochemistry revealed a rare Epstein-Barr-virus-associated polymorphic PTLD. Rarely, PTLD can manifest only with isolated lesions of the duodenal bulb. The course was progressive, going from an incidental finding requiring transfusion anemia to a perforation within 1 month. Repeated endoscopic interventions were unsuccessful. After a surgical intervention the patient died in the course of multiple organ failure. Retrospectively, a reduction of immunosuppression in polymorphic PTLD would have been a treatment option.

[A very rare cause of haemoptysis - coexistence of primary oncocytic adenoma of trachea with bronchial carcinoma]. / Eine äußerst seltene Ursache von Hämoptysen. Koexistenz eines primären onkozytären Adenoms der Trachea und eines Adenokarzinoms des linken Oberlappens.

HISTORY AND ADMISSION FINDINGS: A 70-year-old man with a past history of COPD stage GOLD D with home oxygen therapy and tracheotomy due to long-term ventilation (898 hours) 6 years ago was admitted for investigation of haemoptysis during oral anticoagulation. He suffered from peripheral arterial disease (PAD) with bypass and repeated thrombectomy due to recurrent bypass caps, despite effective warfarin therapy. He had all cardiovascular risk factors. INVESTIGATIONS: The suspicion of a bronchial carcinoma was confirmed by CT. Bronchoscopically a 2 cm lesion in the left upper lobe was biopsied. Additionally, bronchoscopy revealed an approximately erythematous, bloody discolored lesion (diameter 7 mm) at a tracheotomy scar. DIAGNOSIS, TREATMENT AND COURSE: The biopsies revealed an adenocarcinoma in the left upper lobe and an oncocytic adenoma of the trachea - an extremely rare adenoma. The staging result was cT1b cN0 cM0 G2 IASLC Ia. Because of his severe multiple diseases the patient was in an inoperable condition. An interdisciplinary tumor conference recommended an individualized approach with a definitive radiotherapy of the adenocarcinoma. Endoscopic control of the macroscopically completely removed oncocytic adenoma of the trachea shall be performed one year later. CONCLUSIONS: Oncocytoma is an extremely rare adenoma (of the trachea), which in this case, has caused haemoptysis in addition to lung cancer during anticoagulation. For tumor genesis a reactive or hyperplasic response after tracheotomy 6 years ago is considered. Resection is the treatment of choice because of the potential for infiltrative growth. But the decision to treat always depends on individual benefit.

[A very rare submucosal tumour of the rectum - primary endometrioid adenocarcinoma of the rectum wall]. / Ein sehr seltener submuköser Tumor des Rektums - primäres endometrioides Adenokarzinom der Rektumwand.

A 56-year-old female, with a past history of hysterectomy 13 years previously due to uterine myomata, presented with complaints of pain around the anus of a few months duration. Three years previously she underwent a colonoscopy, which was found to be unremarkable. A high suspicion of a submucosal tumour of the rectum in endoscopic examinations was confirmed by endoscopic ultrasound. The biopsy could not specify the tumour characteristics. Based on the diagnosis of a 4 cm submucosal tumour with infiltration of bowel wall and regional lymph nodes the affected segment was resected. Histolopathology revealed an adenocarcinoma involving tissue from the outer bowel wall to the submucosa. However, immunohistochemistry revealed an endometrioid adenocarcinoma, suspicious for primary endometrioid adenocarcinoma of the ovary with rectum metastasis in the absence of a uterus. But this assumption could not be confirmed in the excised ovary. The tumour cells were immunopositive for cytokeratin 7, CA 12 - 5, vimentin and oestrogen receptor, but negative for cytokeratin 20 and CDX-2. Ultimately, we report a very rare case of primary endometrioid adenocarcinoma arising in endometriosis in the rectum wall and presenting as a submucosal tumour.

[Coexistence of multifocal gastric adenocarcinoma with signet-ring cell morphology and a gastrointestinal stromal tumour in a stomach with hp-associated gastritis]. / Multifokales Siegelringzell-Adenokarzinom des Magens mit inzidentellem gastrointestinalem Stromatumor in einer Typ-B-Gastritis.

A 79-year-old man was admitted because of anemia during marcumar therapy with suspected bleeding in the gastrointestinal tract. Endoscopy revealed a large mutifocal poorly differentiated gastric signet ring cell adenocarcinoma. After staging by the usual oesophagogastroduodenoscopic method, a total D 2 gastrectomy was performed. In the pathological resection specimen of the stomach, a multifocal poorly differentiated signet ring cell adenocarcinoma, infiltrating the submucosa (so called early cancer of sm-type) and an incidental gastroinstinal stromal tumour, 0.8 cm in diameter, was diagnosed. This is the first case report of the synchronous occurrence of a multifocal poorly differentiated gastric adenocarcinoma with signet-ring cell morphology (diffuse type according to the Lauren classification) and a GIST incidentally within a stomach with Hp-associated gastritis.

[A rare cause of haematemesis with fatal gastrointestinal bleeding]. / Seltene Ursache einer Hämatemesis mit letalem Ausgang.

A 73-year-old man was admitted to the hospital due to severe hematemesis and collapse, severe anemia and inflammation. Two months ago, the patient had been treated with antibiotics due to septicemia with staphylococcus aureus. At that time CT scan had shown only thoracic arteriosclerosis. The subsequent high urgency upper endoscopy identified a circular mucosal defect in distal esophagus as bleeding origin. The patient died 10 hours after admission. Performing autopsy, a fistula between the thoracic aortic aneurysm and the distal esophagus was found in the background of severe arteriosclerosis. The rapid onset of an aneurysm with rupture after a bacterial infection is typical for a mycotic aneurysm.

[Familial Mediterranean fever. Rare manifestation without fever and with inconspicuous family case history]. / Familiäres Mittelmeerfieber. Seltene Manifestation ohne Fieber und mit unauffälliger Familienanamnese.

HISTORY AND ADMISSION FINDINGS: A 33-year-old man of Turkish descent had suffered from recurrent diffuse abdominal pain and shoulder pain since 13 years. Repeatedly performed investigations in the past had produced numerous diagnoses. The symptoms had been recurring quarterly to weekly, lasted three days on average and resolved spontaneously. He never had fever and the family history was unremarkable. DIAGNOSIS, TREATMENT, AND COURSE: Blood tests demonstrated increased parameters for systemic inflammation and mild normochromic normocytic anemia. In addition to splemomegaly the abdominal computed tomography revealed signs of sacroiliitis. There was no arthritis of the shoulder radiologically. Despite lack of familial history and fever genetic analysis of the Mediterranean fever gene (MEFV) revealed two heterozygous mutations in this MEFV gene for M694 and V726A. The patient was treated with colchicine and has now remained free of symptoms for meanwhile 10 months. There had been no comparable symptom-free period during the last 10 years. CONCLUSION: Sometimes the name "Familial Mediterranean Fever" (FMF) is misleading because this disease may, although rarely, occur without both, fever and familial history. Because of the increasing number of immigrants FMF should be considered in the initial differential diagnosis of patients of Mediterranean origin presenting with abdominal pain. Genetic analysis of the MEFV-gene as well as a therapeutic trial with colchicine, may help to detect FMF.

[Cholangitis with hepatic microabscesses caused by Salmonella enterica serovar choleraesuis]. / Cholangitis mit hepatischen Mikroabszessen durch Salmonella enterica Serovar Choleraesuis.

HISTORY AND ADMISSION FINDINGS: A 71-year-old man was admitted to the emergency unit of another hospital with a mild gastroenteritis and high fever. On admission g-GT and C-reactive protein (CRP) levels were markedly elevated. Under nonspecific antibiotic therapy with ampicillin/sulbactam the fever persisted and for the first time, on day 5, the patient complained of right-sided abdominal pain. An increase in the laboratory values indicated cholestasis. After changing the antibiotics to ceftriaxon and metronidazole, acute cholangitis being suspected, the fever subsided immediately and the CRP level decreased. The patient was discharged after seven days of antibiotic treatment. But he was once more admitted after four weeks to another hospital because of severely reduced general condition and mild fever. He was transferred to our unit after two weeks. INVESTIGATIONS AND DIAGNOSIS: The test values indicated cholestasis and CRP was markedly elevated, while aminotransferase activity was slightly increased and normocytic normochromic anemia developed. Viral hepatitis, autoimmune and metabolic liver diseases, toxic liver damage, extrahepatic cholestasis and an endocarditis were excluded. Bile was aspirated by endoscopic retrograde cholangiopancreatography and added to blood culture bottles. Salmonella enterica serovar choleraesuis var. Kunzendorf was isolated. TREATMENT AND FURTHER COURSE: The patient was treated with ciprofloxacin, 2 x 250 mg by mouth for a total of five weeks. After 17 days of treatment no Salmonella bacteria were grown from a newly aspirated bile sample and the patient became free of fever. CONCLUSION: Salmonella infections do not always present as gastroenteritis. Bacteremia should be considered in the differential diagnosis of such infections. If cholangitis persists, the aspiration of bile for microbiological tests can be a rational diagnostic step and facilitates treatment. Prolonged administration of antibiotics is necessary to avoid relapse. and follow-up is very important when treatment is finished.

Reduction of infarct size by selective stimulation of prostaglandin EP(3)receptors in the reperfused ischemic pig heart.

We have previously identified prostaglandin EP(3)receptors in left ventricular myocardium. To assess the potential contribution of this receptor subtype to the anti-ischemic properties of E-type prostaglandins (i.e. PGE(1)), two groups of anesthetized open-chest minipigs were subjected to LAD occlusion (1 h) and reperfusion (3 h). In one group, the selective EP(3)receptor agonist M&B 28.767 (2 pmol/kgxmin) was infused into the LAD from 20 min before ischemia until the end of reperfusion. The other group received vehicle. M&B 28.767 did not alter the systemic hemodynamics, but significantly reduced infarct size (tetrazolium staining) and creatine kinase release by 53% and 48%, respectively. Ischemia-induced ventricular arrhythmias were mostly reduced. Further experiments analysed the effects of EP(3)receptor stimulation on normoxic myocardium. PGE(1), an unselective agonist to all EP receptor subtypes, as well as M&B 28.767 (2 pmol/kgxmin of each into the LAD) reduced the action potential duration (epicardial monophasic electrodes) and almost prevented the inotropic response to intravenous isoprenaline. This dual response is consistent with the EP(3)receptor coupling to an inhibitory G protein. This was confirmed in separate experiments with stable Chinese hamster ovary cell transfectants expressing the porcine EP(3)receptor, where M&B 28.767 inhibited the forskolin-induced increase in cAMP in a concentration-dependent manner. It is concluded that the protection of reperfused ischemic myocardium by E-type prostaglandins is mediated by EP(3)receptors, which seems to involve a combined activation of repolarizing membrane currents and an inhibition of deleterious effects caused by ischemia-induced catecholamine release.

[Experimental study of the effect of pentaerythritol tetranitrate in acute myocardial infarct]. / Experimentelle Untersuchungen zur Wirkung von Pentaerithrityltetranitrat bei akutem Myokardinfarkt.

Pentaerithrityltetranitrate (PETN) is an organic nitrate ester with high selectivity to venous vessels and little development of tolerance. Here we report experimental results concerning the hemodynamic and antiischemic effects of intravenously administered PETN. The experiments were performed with anesthetized, open-chest minipigs (25 to 35 kg body weight [bw]). PETN (0.125, 0.25, 0.5 mg/kg bw, i.v.) dose-dependently decreased left ventricular systolic pressure without change in peripheral vascular resistance. A reflex increase in heart rate returned to normal within 20 minutes (0.125 and 0.25 mg/kg). PETN (0.5 mg/kg) also transiently (10 minutes) decreased left ventricular contractility. In additional experiments, myocardial infarction was induced by LAD occlusion (1 hour), followed by reperfusion (3 hours). PETN (0.6 mg/h, i.v.) was administered starting 20 minutes before ischemia until the end of reperfusion. While PETN did not cause hemodynamic changes, infarct size was significantly decreased compared with vehicle (56 +/- 6% vs 83 +/- 3% of area at risk, p < 0.05). Regional contractile function (ultrasound crystals) was completely abolished during ischemia and did not recover during 3 hours reperfusion in control hearts. However, PETN-treated pigs showed partial functional recovery (19 +/- 5%, p < 0.05 vs vehicle) during the first hour of reperfusion. Histologic evaluation revealed a decreased number of granulocytes accumulated in the ischemic myocardium of PETN-treated animals. Accordingly, in-vitro experiments showed a reduction by PETN of the adherence of HL-60 cells differentiated to granulocytes to vascular smooth muscle cells. Therefore, PETN reduced infarct size and improved myocardial function after LAD occlusion and reperfusion. It is concluded that the intravenous administration of PETN might be of advantage in the treatment of acute myocardial ischemia.

Quantitative analysis of neurofibromatosis type 2 gene transcripts in meningiomas supports the concept of distinct molecular variants.

Meningiomas frequently show mutational inactivation of the neurofibromatosis type 2 tumor suppressor gene (NF2 gene). In a previous study, mutations were preferentially observed in the fibroblastic and transitional subtypes (75%), whereas the meningothelial variant was significantly less affected (25%). To study a potential role of the NF2 gene on the transcriptional level, we have analyzed NF2 transcripts in 67 meningiomas of different subtypes. A competitive reverse transcriptase-PCR assay with an external NF2 gene standard was used for quantitative mRNA analysis. Fibroblastic and transitional meningiomas exhibited significantly lower levels of NF2 mRNA compared with meningothelial variants (p = 0.001, unpaired t test). These data support the concept of a distinct molecular pathway in the formation of meningothelial meningiomas independent from the NF2 gene or its gene product merlin/schwannomin. In addition, in these tumors, NF2 expression was reduced by a factor of 10 (p < 0.001, unpaired t test) in those meningiomas with NF2 gene mutations suggesting decreased stability or impaired transcription of mutated NF2 mRNA. In conclusion, our data provide further evidence for molecular differences between subtypes of meningiomas and support an NF2-independent pathogenesis of meningothelial meningiomas.

[Risk of neonatal acidosis and maternal respiration during labor]. / Neonatales Azidose-Risiko und mütterliche Atmung sub partu.

BACKGROUND: The reported incidence of neonatal acidosis varies++ significantly in different obstetrical departments. We wanted to investigate to which extend neonatal acidosis is depended on maternal respiration patterns during the third stage of labor. METHODS: Maternal arterial blood gas analysis was performed in 101 term pregnancies. Fetal acid-base parameters from arterial and venous umbilical blood were assessed simultaneously. SPEARMAN rank correlation (rs) was used to investigate the statistical relationship of maternal and fetal blood gas parameters and pH-values. Moreover a computer model was developed to describe the influence of maternal respiration on neonatal acidotic risk figures. RESULTS: A highly significant correlation was established between corresponding variables in maternal arterial blood and in venous umbilical blood (rs > or = 0.500, 2P < 0.001). These correlations were not as striking when comparing maternal parameters with corresponding variables in arterial umbilical blood. The partial oxygen pressure in arterial and venous umbilical blood did not show any correlation with the variables of the maternal acid-base status. In the computerized simulation model mild maternal hyperventilation during the third stage of labor decreased the risk of neonatal acidosis (pH, UA < 7.100%) by approximately 25% without evidence of lack of fetal oxygen supply. CONCLUSIONS: A mild maternal hyperventilation synchronized with uterine contractions during the third stage of labor in combination with rapid breathing when delivering the fetal head has a favourable influence on the neonatal acid-base balance. In this study there is no indication that such an obstetrical management results merely in a laboratory artifact, because according to our data there was indeed no indication of compromised fetal oxygen supply. Routine fetal blood sampling also from venous umbilical blood appears to be useful in differentiating between combined feto-maternal and isolated fetal variations in actual pH-values.