Question: A 26-year-old woman presented with abdominal pain, nausea, and vomiting. Her history revealed episodes of abdominal pain over the past 5 years, and bloating and diarrhea lasting approximately 2 days without an obvious nutritional precipitant. She had been classified as having irritable bowel syndrome, because previous investigations including endoscopy (in the interval) never retrieved pathologic findings. Her medical history revealed that she did not take any medication except an oral contraceptive. The physical examination showed neither defense nor any sign of local or generalized peritonism. In the laboratory the d-dimer level was found massively elevated (28.02 μg/mL; normal level, <0.50). Thus, computed tomography was performed and demonstrated massive swelling of the complete small bowel (Figure A, arrows). What is the most likely diagnosis? Look on page 371 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Initially, a thrombosis of the mesenteric veins was suspected, but this diagnosis was not in any way compatible with the relatively good clinical condition of our patient. She was managed conservatively and improved within 24 hours. After ultrasound examination of the intestine 2 days later, the bowel wall appeared to not be thickened any more. Self-remitting abdominal pain without clear organic etiology that is recurrent and lasts >6 hours is a clinical criterion for HAE defined by a European working group.1Agostoni A. Aygoren-Pursun E. Binkley K.E. et al.Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond.J Allergy Clin Immunol. 2004; 114: S51-S131Abstract Full Text Full Text PDF PubMed Scopus (587) Google Scholar This criterion was met precisely by our patient. Thus, HAE was very likely. She experienced an episode of a facial angioedema some years ago. In addition, her family history shows cases of facial angioedemas, partially associated with angiotensin converting enzyme inhibitor intake. HAEs are subdivided into 3 types: Type I HAE is characterized by low levels and reduced functional tests of C1 esterase inhibitor, whereas type II HAE shows normal levels but reduced function of C1 esterase inhibitor. Type III HAE, which affects nearly exclusively females in an estrogen-dependent fashion (precipitation or worsening of symptoms during pregnancy, treatment with oral contraceptives, or hormonal replacement therapy) shows normal levels as well as normal function of C1 esterase inhibitor. It has been demonstrated that a gain in function mutation leading to increased activity of coagulation factor XII (FXII) leading to enhanced kinin production causes HAE type III.2Bork K. Wulff K. Hardt J. et al.Hereditary angioedema caused by missense mutations in the factor XII gene: clinical features, trigger factors, and therapy.J Allergy Clin Immunol. 2009; 124: 129-134Abstract Full Text Full Text PDF PubMed Scopus (166) Google Scholar The estrogen dependency is explained by the fact that the expression of FXII is increased by estrogens via estrogen-responsive elements in the promoter region.3Farsetti A. Misiti S. Citarella F. et al.Molecular basis of estrogen regulation of the Hageman factor XII gene expression.Endocrinology. 1995; 136: 5076-5083Crossref PubMed Scopus (96) Google Scholar In our patient, C3 and C4 levels as well as the level of C1 esterase inhibitor in functional testing were normal. Thus, the diagnosis was hereditary angioedema with normal C1 inhibitor levels. Our patient improved spontaneously after symptomatic therapy within 2 days. Avoidance of estrogen-containing oral contraceptives was recommended and no episodes were observed in the next several months. A clinical relapse after 6 months was again associated with the intake of an oral contraceptive.

A 36-year old man was referred to our hospital with intermittent abdominal pain and bloating. Routine gastroduodenoscopy and ileocolonoscopy were performed without any visible signs of pathologic gastric, duodenal, ileal, or colonic mucosa. Routine biopsies were taken from gastric antrum and corpus, proximal duodenum, distal ileum, and from 4 different stages of the colon (ascending, transverse, descending, and sigmoid colon). All biopsies were from macroscopic intact mucosa without any bleeding evidence or visible signs for acute perforation. After an inconspicuous 2-hour observation period the patient was sent home. On the following day the patient returned to our hospital complaining about intense left-sided chest pain with radiation into his left arm. The patient reported that slight chest pain started about 8 hours after demission and worsened over night. On clinical examination, both lung sides were clear on auscultation without signs for pneumothorax, no subcutaneous thoracic emphysema was noted, heart sounds were normal, and the stomach was tender on palpation without any signs of peritonitis. An electrocardiogram, cardiac enzymes, and D dimer were within normal limits. Because of free mediastinal, pericardial, and retroperitoneal air, diagnosis of pneumomediastinum (white arrows, Figure A), pneumopericardium (black arrow, Figure A), and retropneumoperitoneum (white arrow, Figures B and C) was made. The patient was admitted for clinical observation and was designated as nothing per oral for 48 hours. Prophylactic antibiotic therapy (piperacilline/tazobactam) and pain therapy were started. Computed tomography of the chest and abdomen showed no signs for abscess formation. Follow-up x-rays showed gradual reabsorption of free retroperitonal, mediastinal, and pericardial air. Histologic biopsy examinations were normal. After a hospital stay of 4 days, the patient was discharged symptom-free. Retroperitoneal perforation is a rare complication after colonoscopy and gastroduodenoscopy, ranging between 0.1%–1%. Whereas several case reports were found in literature concerning retroperitoneal perforation after endoscopic gastrointestinal examination associated with polypectomy, mucosectomy, or in patients with active inflammatory bowel diseases or colonic cancer, there were only few reports about perforations during routine endoscopic examination and biopsy taking.1Girardi A. Piazza I. Giunta G. et al.Retroperitoneal, mediastinal and subcutaneous emphysema as a complication of routine upper gastrointestinal endoscopy.Endoscopy. 1990; 22: 83-84Crossref PubMed Scopus (20) Google Scholar Possible places for perforation in our case could have been the biopsy sites in the duodenum, ileum, ascending or descending colon. All these parts have total (duodenum) or partial (ileum, ascending/descending colon) retroperitoneal position. In contrast to intraperitoneal perforation with acute peritonitis symptoms and easy recognition on x-ray, retroperitoneal perforation shows initially fewer symptoms and can be easily overlooked on x-ray.2Bejvan S.M. Godwin J.D. Pneumomediastinum: old signs and new signs.AJR Am J Roentgenol. 1996; 166: 1041-1048Crossref PubMed Scopus (175) Google Scholar Most cases can be managed conservatively; a surgical intervention in patients without signs of peritonitis is seldom necessary.3Igbal C.W. Chun Y.S. Farley D.R. Colonoscopic perforations: a retrospective review.J Gastrointest Surg. 2005; 9: 1229-1235Crossref PubMed Scopus (129) Google Scholar

Background Cheilitis granulomatosa and Melkersson-Rosenthal syndrome are both rare and benign diseases. Because of their granulomatous character, a relationship to Crohn's disease has been suggested. Furthermore, because of their unknown aetiology, treatment is difficult, and evaluation of response is hampered by the natural tendency to spontaneous resolution and recurrence.Objectives and methods To evaluate gastrointestinal involvement by clinical history, conventional endoscopy, and capsule endoscopy as well as to compare efficacy of treatment modalities on a series of 14 patients, one of the biggest collectives reported.Results Four patients (4 of 14) were previously, simultaneously, or subsequently diagnosed with Crohn's disease. In six patients (6 of 14) with minor gastrointestinal symptoms as flatulence, occasional constipation, diarrhoea, or admixture of mucus with the stool, we could not detect any signs of inflammatory bowel disease by capsule endoscopy. Nine patients received clofazimine, and eight patients responded to treatment (four complete responses, four partial responses). Two patients were successfully treated with infliximab. Systemic methylprednisone was not successful in two patients.Conclusions Close to 30% of patients showed an association of cheilitis granulomatosa and Crohn's disease. Forty-three per cent of patients reported minor gastrointestinal irregularities without any detectable changes of Crohn's disease. Clofazimine seems to be an effective treatment, although long-term application is necessary with frequent aggravation in the beginning. Infliximab, an effective drug in Crohn's disease, could be a promising treatment option for severe cases.

Question: A 22-year-old woman was referred to our outpatient clinic by her general practitioner with chest pain for further examination. The woman complained of retrosternal pain for several days with aggravation during intake of fluids and meals (odynophagia). She had no fever or cough; throat inspection revealed no pathologic findings. Her lungs were clear on auscultation without pleural rubs. Heart sounds were normal without any murmurs. Chest x-ray was normal. Gastroscopy with histopathologic examination of biopsies from the middle third of the esophagus showed the following findings (Figures A and B). What is the most likely diagnosis ? Look on page 1365 for the answer and see the Gastroenterology website (http://www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Circular esophagitis with a normal surrounding mucosa sparing the distal and proximal part of the esophagus (Figure A) was observed during endoscopy in our case. Hematoxylin and eosin stained biopsies show ulceration with a mixed inflammatory infiltrate (Figure B). A thorough case history revealed that the patient was taking doxycycline pills 100 mg twice a day for acne for more than three weeks. We treated the patient with a solution containing the local anesthetic oxetacaine and doxycycline intake was discontinued. The patient was immediately able to swallow without pain. Because of the good response to treatment with disappearance of all symptoms a control gastroscopy was not performed. Pill esophagitis seems to be more common than expected especially in young women taking doxycycline capsules,1Kadayifci A. Gulsen M.T. Koruk M. Savas M.C. Doxycycline-induced pill esophagitis.Dis Esophagus. 2004; 17: 168-171Crossref PubMed Scopus (62) Google Scholar but it is also associated with nonsteroidal anti-inflammatory drugs, slow-release forms of potassium chloride, ferrous sulphate, and some other drugs.2Jaspersen D. Drug-induced oesophageal disorders: pathogenesis, incidence, prevention and management.Drug Saf. 2000; 22: 237-249Crossref PubMed Scopus (126) Google Scholar Common places to find ulcerations from pill esophagitis are where there is anatomic narrowing, including the arch of the aorta, the left mainstem bronchus, and the gastroesophageal junction. Dissolved doxycycline produces an acid solution (pH < 3) that causes esophageal mucosal injury when esophageal transit time is increased.3Kikendall J.W. Pill esophagitis.J Clin Gastroenterol. 1999; 28: 298-305Crossref PubMed Scopus (137) Google Scholar The main reasons for an increased transit time are pill intake with little or no fluid prior to bedtime followed by recumbency (like in our case), decreased production of saliva (associated with older age, intake of anticholinergics, connective tissue diseases), and galenic formulation (increased transit time was shown 3 times as often in doxycycline capsules as in doxycycline tablets).4Petersen K.U. Jaspersen D. Medication-induced oesophageal disorders.Expert Opin Drug Saf. 2003; 2: 495-507Crossref PubMed Scopus (20) Google Scholar A Medline search revealed 31 case reports of esophagitis linked to the intake of doxycycline and the WHO adverse drug reaction (ADR) database has 352 suspected reports of doxycycline-induced esophagitis for the period 1969 to 2003.5http://www.hsa.gov.sg/docs/safetyalert_doxycycline_Mar04.pdf.Google Scholar Patients with this type of injury typically take their medication with a small amount of water immediately before going to bed. They may then wake up several hours later with severe retrosternal chest pain and odynophagia. This could be prevented by swallowing the pills with enough liquid and remaining in the upright position thereafter.6Baeriswyl G. et al.Importance of drug-induced ulceration in endoscopic lesions of the esophagus.Schweiz Med Wochenschr. 1985; 19: 6-9Google Scholar We thank Prof Dr J. Krugmann, Department of Pathology at the University Innsbruck for the histopathologic image.

Am 1. März 2004 haben wir mit der Durchführung von Doppelballonenteroskopien begonnen. Die Indikation für die Durchführung der Untersuchung wurde bei uns aufgrund der geringen Erfahrungslage in Europa restriktiv gestellt. In der Zwischenzeit wurden an 10 Patienten insgesamt 13 Untersuchungen vorgenommen. Das mittlere Alter der Patienten war 67,1 (42–90) Jahre. 7/13 Untersuchungen wurden transgastral 6/13 transanal vorgenommen. Der mittlere Vorschub im Dünndarm betrug dabei 245 (170–300) bzw. 147 (0–230)cm. Bei 9/10 Patienten wurde die Indikation zur Doppelballonenteroskopie (DBE) nach einer M2A-Capsule-Endoskopie (CE) gestellt, und der Zugangsweg (transgastral bzw. transanal) durch den in der CE gestellten Befund gewählt. Bei 9/10 Patienten war eine Blutungsquelle im Dünndarm vermutet worden [4/9 V. a. Angiodysplasie (AD), 3/9 V. a. Polyp oder Tumor 2/9 unklare aktive Blutung]. Die AD konnten in allen Fällen bestätigt und in der gleichen Sitzung thermisch koaguliert werden. Die in der CE vermuteten Polypen bzw. Tumore konnten in der DBE nicht bestätigt werden. Es gab bisher keine schweren Komplikationen, eine Patientin wurde jedoch einen Tag nach der Untersuchung mit einer peritonealen Reizung, welche unter konservativer Therapie ausheilte. Das klinische Outcome (Abnahme der Transfusionsbedürftigkeit, Besserung der Anämie etc.) lässt sich derzeit aufgrund der geringen Fallzahl und des kurzen Beobachtunszeitraumes noch nicht abschätzen, lediglich bei einem Patienten musste die thermische Koagulation nach 9 Monaten wiederholt werden, nachdem sich neue Angiodysplasien gebildet hatten. Kontrollierte Studien werden noch den Stellenwert der DBE im endoskopischen Spektrum festigen müssen, insbesonders gilt es zu klären, ob die Vorschaltung einer CE einen klinischen und ökonomischen Vorteil bietet.

Endogenous retroviruses in humans are discussed as putative etiologic agents in tumorigenesis. Molecular mimicry of cellular epitopes by retroviruses may be of importance for the genesis of autoimmune diseases. A group of human endogenous retroviruses, HERV-K, which is related to the mouse mammary tumour virus, has been characterised previously and open reading frames have been found covering their gag, pol, prt and env genes. Transcription of HERV-K genomes at the mRNA level as well as antibodies in human sera directed against HERV-K env have been detected recently. We have generated a monoclonal antibody (mAb), anti-HERV1, against a recombinant HERV-K Env protein. This mAb is capable of immunoprecipitating a 67-kD glycoprotein from the human breast carcinoma cell line T47D, the amount of which is strongly enhanced after stimulation with estradiol followed by progesterone. The same band could be precipitated from other carcinoma cell lines (Hep2, MCF7 and HeLa), but not from the human B-lymphoblastoid cell line Raji and from cultured human fibroblasts. Incubation of this antigen in the presence of endoglycosidase F indicates the presence of N-linked carbohydrate moieties of at least 7-9 kD.

The distribution of the human endogenous retrovirus (HERV)-K genome was investigated by Southern-blot analyses using a HERV-K-env DNA probe. With the exception of one DNA-sample, obtained from a Chinese individual in whom an amplification of HERV-K was detected, Southern-blot analyses yielded identical hybridization patterns with DNA from peripheral blood lymphocytes of 37 normal healthy blood donors, with DNA from six tumor cell lines, or with 23 DNA samples prepared from various carcinoma tissues. To elucidate whether the integration of HERV-K genomes into the primate lineage occurred as a single event or as an integration with later expansion, we further examined the evolutionary history of HERV-K by Southern blot analyses with DNA samples from different primate species. We detected HERV-K genomes in Macaca mulatta and Macaca silenus, which represent Old World monkeys, but not in prosimians (Galago demidovii) and New World monkeys, represented by Saguinus fuscicollis, Saguinus oedipus, and Callithrix iacchus. Thus, we assume that the infection of the primate lineage with HERV-K had occurred after the divergence of New World and Old World monkeys, but before the evolutionary expansion of large hominoids. In contrast to the apparent lack of HERV-K-env sequences in DNA from tissue of the New World monkey Saguinus oedipus (cotton-top marmoset), we found HERV-K-DNA in the B95-8 cell-line, which is a Saguinus oedipus leukocyte cell-line, immortalized in vitro by Epstein-Barr virus (EBV) and cultivated in human cells. It may be speculated that HERV-K-DNA or HERV-K-particles were introduced into these cells during in vitro transformation with EBV.

AIDS Research and Human RetrovirusesVol. 11, No. 7 Human Endogenous Retrovirus K Does Not Encode Mouse Mammary Tumor Virus-Related Antigens in Human Breast CarcinomasWERNER VOGETSEDER, JOACHIM DENNER, KLAUS BOLLER, REINHARD KURTH, and MANFRED P. DIERICHWERNER VOGETSEDERSearch for more papers by this author, JOACHIM DENNERSearch for more papers by this author, KLAUS BOLLERSearch for more papers by this author, REINHARD KURTHSearch for more papers by this author, and MANFRED P. DIERICHSearch for more papers by this authorPublished Online:16 Mar 2009https://doi.org/10.1089/aid.1995.11.869AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited ByOf mice, cats, and men: Is human breast cancer a Zoonosis?1 January 2005 | Microscopy Research and Technique, Vol. 68, No. 3-4Expression and Functions of Human Endogenous Retroviruses in the Placenta: An UpdatePlacenta, Vol. 25 Volume 11Issue 7Jul 1995 To cite this article:WERNER VOGETSEDER, JOACHIM DENNER, KLAUS BOLLER, REINHARD KURTH, and MANFRED P. DIERICH.Human Endogenous Retrovirus K Does Not Encode Mouse Mammary Tumor Virus-Related Antigens in Human Breast Carcinomas.AIDS Research and Human Retroviruses.Jul 1995.869-872.http://doi.org/10.1089/aid.1995.11.869Published in Volume: 11 Issue 7: March 16, 2009PDF download

Human endogenous retrovirus (HERV) K is present in about 50 copies in the human genome and transcription of HERV-K has previously been detected in several tumor cell lines as well as in peripheral blood lymphocytes from healthy donors. By means of immunoblotting we investigated the presence of antibodies recognizing recombinant HERV-K-envelope outer membrane constructs in different serum collectives. A total of 12.6% of sera obtained from normal blood donors was found positive. In serum collectives from breast carcinoma patients, HIV-1-positive individuals, and persons with cytomegalovirus infections no significant difference from the normal blood donor serum collective could be observed. Only a group of persons with a repeatedly raised serum neopterin concentration (> 10 nmol/liter) of unknown cause (HIV and hepatitis B and C virus infections were excluded) showed a significant higher percentage of HERV-K-outer membrane envelope-positive sera (21%). Furthermore we could observe a parallel HIV-1/HERV-K seroconversion, which probably is not due to an HIV-1/HERV-K-outer membrane envelope cross-reactivity. Possible implications of these findings are discussed.