[A 3-week history of intestinal symptoms in a 67-year-old male patient with chronic arthralgia]. / Seit 3 Wochen bestehende intestinale Beschwerden bei einem 67-jährigen Patienten mit chronischen Arthralgien.

Whipple disease is an infection caused by the bacterium Tropheryma whipplei. Due to its unspecific clinical symptoms, it is difficult to diagnose and often remains undetected for a long time. The case of a patient who presented with acute intestinal symptoms to the authors' department is reported. The diagnosis of classic Whipple disease was established. The symptoms subsided under antibiotic therapy. Complications in the form of immune reconstitution inflammatory syndrome (IRIS) occurred, requiring immunosuppressive treatment.

[Implementation of Workplace Health Promotion/Workplace Health Management in Germany: State-of-the Art and Need for Further Research]. / Umsetzung Betrieblicher Gesundheitsförderung/Betrieblichen Gesundheitsmanagements in Deutschland: Stand und Entwicklungsbedarfe der einschlägigen Forschung.

AIM: The data on health management programmes in German companies show quite heterogeneous results. The aim of the study was to gain more transparency into the cause of these discrepancies as well as information on factors influencing the willingness of companies to implement such programmes. METHODS: Based on a systematic database search, relevant studies were identified and comparative analysis of their contents was carried out. RESULTS: The existing studies on the health management programmes in German companies reveal significant discrepancies in terms of their research question, representativeness, approach and design. Nevertheless, they do reveal certain trends identifying significant factors that influence the willingness of companies to implement such programmes. CONCLUSION: In the design of future studies to analyse the distribution of corporate health management programmes, there is a need to agree on common definitions and data collection methods and how the results are to be categorised. When evaluating the effects of corporate programmes, the quantitative data would need to be supplemented with qualitative data that would be capable of identifying how such programmes are implemented and the associated organisation-specific cultural patterns.

Severe disease presentation and poor outcomes among pediatric systemic lupus erythematosus patients in South Africa.

Background Systemic lupus erythematosus (SLE) is a life-threatening multisystem autoimmune disease that is more severe in patients of African ancestry and children, yet pediatric SLE on the African continent has been understudied. This study describes a cohort of pediatric SLE (PULSE) patients in South Africa. Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were enrolled in this cross-sectional study from September 2013 to December 2014. Information on clinical and serological characteristics was extracted from medical records. Results were compared to a well-described North American pediatric SLE cohort. Results Seventy-two South African patients were enrolled in the study; mean age 11.5 years; 82% were girls. The racial distribution was 68% Coloured, 24% Black, 5% White and 3% Asian/Indian. Most patients presented with severe lupus nephritis documented by renal biopsy (61%). Of patients with lupus nephritis, 63% presented with International Society of Nephrology/Renal Pathology Society class III or IV. Patients in the PULSE cohort were more likely to be treated with cyclophosphamide, methotrexate and azathioprine. The PULSE cohort had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K) 20.6). The SLEDAI-2K at enrolment in the PULSE cohort (5.0) did not differ from the North American pediatric SLE cohort (4.8). Sixty-three per cent of the PULSE cohort had end organ damage with Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI) score >0 (mean SLICC-DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE cohort, nine (13%) developed end-stage renal disease with six (8%) requiring transplant, strikingly higher than North American peers (transplant rate <1%). Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis and significant disease damage at enrolment in the South African registry. South African patients have severe lupus nephritis and poor renal outcomes compared to North American peers. Our study revealed a severe disease phenotype in the PULSE cohort resulting in poor outcomes in this high-risk population.

[Strengthening Public and Global Health in Germany - an Appraisal of the Statement "Public Health in Germany" by the German Scientific Academies from June 16th 2015]. / Public und Global Health in Deutschland stärken - Eine Einordnung der Stellungnahme "Public Health in Deutschland" der wissenschaftlichen Akademien vom 16.6.2015.

In June 2015 the scientific academies "Leopoldina" and "acatech" and the union of the German academies of sciences and humanities published a statement on public and global health in Germany. The statement contains many valuable albeit generic and well-known recommendations. The few specific recommendations focus on centralizing research while weakening the role of universities and on the relative increase of research on public health genomics. These recommendations are not based on empirical or theoretical analyses and risk subverting successful developments of the recent past. To actually strengthen public and global health in Germany the existing institutions need to be backed up while designated funding of public and global health needs to be extended.

Accumulation of small hyaluronan oligosaccharides in tumour interstitial fluid correlates with lymphatic invasion and lymph node metastasis.

BACKGROUND: Association studies have implicated the glycosaminoglycan hyaluronan (hyaluronic acid, HA) and its degrading enzymes the hyaluronidases in tumour progression and metastasis. Oligosaccharides of degraded HA have been ascribed a number of biological functions that are not exerted by high-molecular-weight HA (HMW-HA). However, whether these small HA oligosaccharides (sHA) have a role in tumour progression currently remains uncertain due to an inability to analyse their concentration in tumours. METHODS: We report a novel method to determine the concentration of sHA ranging from 6 to 25 disaccharides in tumour interstitial fluid (TIF). Levels of sHA were measured in TIF from experimental rat tumours and human colorectal tumours. RESULTS: While the majority of HA in TIF is HMW-HA, concentrations of sHA up to 6 µg ml(-1) were detected in a subset of tumours, but not in interstitial fluid from healthy tissues. In a cohort of 72 colorectal cancer patients we found that increased sHA concentrations in TIF are associated with lymphatic vessel invasion by tumour cells and the formation of lymph node metastasis. CONCLUSIONS: These data document for the first time the pathophysiological concentration of sHA in tumours, and provide evidence of a role for sHA in tumour progression.

[Situation and perspectives of public health in Germany--research and teaching. Position paper of the German Public Health Association]. / Situation und Perspektiven von Public Health in Deutschland--Forschung und Lehre. Positionspapier der Deutschen Gesellschaft für Public Health e. V.

This position paper of the German Public Health Association describes current situation and perspectives of public health in Germany with emphasis on research and teaching. It outlines those measures necessary for strengthening of public health research in Germany.

[Histopathological diagnosis and differential diagnosis of colorectal serrated polys: findings of a consensus conference of the working group "gastroenterological pathology of the German Society of Pathology"]. / Histopathologische Diagnostik und Differenzialdiagnostik serratierter Polypen im Kolorektum : Ergebnisse einer Konsensuskonferenz der AG "Gastroenterologische Pathologie der DGP"

Until recently, two major types of colorectal epithelial polyps were distinguished: the adenoma and the hyperplastic polyp. While adenomas - because of their cytological atypia - were recognized as precursor lesions for colorectal carcinoma, hyperplastic polyps were perceived as harmless lesions without any potential for malignant progression, mainly because hyperplastic polyps lack cytological atypia. Meanwhile, it is evident that the lesions formerly classified as hyperplastic represent a heterogeneous group of polyps, some of which exhibit a significant risk of neoplastic progression. These lesions show characteristic epigenetic alterations not commonly seen in colorectal adenomas and progress to colorectal carcinoma via the so-called serrated pathway (CIMP pathway). This group of polyps is comprised not only of hyperplastic polyps, but also of sessile serrated adenomas (SSA), traditional serrated adenomas (TSA) and mixed polyps, showing serrated and "classical" adenomatous features. In a consensus conference of the working group of gastroenterological pathology of the German Society of Pathology, standardization of nomenclature and diagnostic criteria as well as recommendations for clinical management of these serrated polyps were formulated and are presented herein.

Juvenile idiopathic arthritis flare due to rice bodies in the knee of a 10-year-old girl.

A 10-year-old girl with juvenile idiopathic arthritis in remission presented with a flare of her arthritis. All her joints responded to treatment except the right knee, despite the use of disease-modifying antirheumatic drugs, non-steroidal anti-inflammatory medication and high-dose cortisone. A magnetic resonance imaging scan showed a knee densely packed with rice bodies. After surgical removal of the rice bodies the inflammation settled once again, and the patient remains well on her usual medication.

Estrogen inhibits the response-to-injury in a mouse carotid artery model.

The atheroprotective effects of estrogen are well documented, but the mechanisms responsible for these effects are not well understood. To study the role of physiologic (nanomolar) estrogen levels on the arterial response-to-injury, we applied a mouse carotid artery injury model to ovariectomized C57BL/6J mice. Mice were treated with vehicle (-E2, n = 10) or 17 beta-estradiol (+E2, n = 10) for 7 d, subjected to unilateral carotid injury, and 14 d later contralateral (normal = NL) and injured carotids from -E2 and +E2 animals were pressure fixed, harvested, and analyzed by quantitative morphometry. E2 levels in +E2 mice were consistently in the nanomolar range (2.1-2.5 nM) at days 0, 7, and 14. At 14 d, measures of both intimal and medial area were markedly increased in the -E2 group: (-E2 vs NL, P < 0.05 for both), but were unchanged from normal levels in the +E2 group (+E2 vs NL, P = NS and +E2 vs -E2, P < 0.05 for both). Cellular proliferation, as assessed by bromodeoxyuridine (BrdU) labeling, was significantly increased over NL in the -E2 mice, but this increase was markedly attenuated in the estrogen replacement group (total BrdU positive cells/section: NL = 6.4 +/- 4.5; -E2 = 113 +/- 26, +E2 = 40 +/- 3.7; -E2 vs NL, P < 0.05; +E2 vs NL, P = NS; -E2 vs +E2, P < 0.05). These data (a) demonstrate significant suppression of the mouse carotid response-to-injury by physiologic levels of estrogen replacement; (b) support the utility of this model in the study of the biologic effects of estrogen on the vascular-injury response; and (c) suggest a direct effect of estrogen on vascular smooth muscle cell proliferation in injured vessels.

[Solitary fibrous tumor in the tongue: case report and review of the literature]. / Solitärer fibröser Tumor der Zunge: Fallbericht und Literaturübersicht.

Solitary fibrous tumors (SFT) are rare, mostly fibroblastic tumors usually situated in the pleura. Extrapleural manifestations have been described. However, the oral cavity is an uncommon localisation of this tumor. We report the very unusual case of an SFT affecting the tongue that could be removed completely because of its clear delineation. Intraoperative incisional biopsies were used to exclude malignancy. For definitive classification of the tumor, additional histopathologic examinations had to be carried out. Because SFT exhibit malignant behavior only in exceptional cases and their recurrence after complete removal has never been encountered, surgery can focus on the preservation of undisturbed function of the tongue.

Exopolysaccharide-producing Streptococcus thermophilus CRL1190 reduces the inflammatory response caused by Helicobacter pylori.

This work evaluated the ability of the probiotic Streptococcus thermophilus CRL1190 strain and its exopolysaccharides to adhere to gastric mucosa. Probiotic bacteria attachment to the human stomach epithelium was confirmed in human stomach tissue samples and the gastric epithelial cell line AGS. In addition, it was demonstrated that S. thermophilus CRL1190 strain reduced Helicobacter pylori adhesion and attenuated inflammatory response in AGS cells. This is the first demonstration of the capacity of S. thermophilus CRL1190 to adhere to the stomach gastric mucosa, and improve protection against H. pylori through the reduction of its adhesion and the modulation of the inflammatory response. Therefore, S. thermophilus CRL1190 fermented milk is a good candidate for further in vivo studying of the protective effect of functional food against H. pylori infection and gastric inflammatory damage.

Long-term acid suppression by omeprazole in gastro-oesophageal reflux disease patients does not lead to anti-gastric autoantibody production.

BACKGROUND: Helicobacter pylori-associated atrophy of the gastric corpus is associated with the presence of anti-canalicular autoantibodies. Also, long-term profound acid suppression in H. pylori-infected subjects may cause atrophic corpus gastritis. AIM: To investigate whether long-term acid suppression by omeprazole leads to antigastric autoantibodies. METHODS: Fifty patients, of which 34 H. pylori-positive on entry of the study, were treated with omeprazole (20-40 mg once daily) for reflux oesophagitis, and were evaluated for anti-gastric autoantibody responses by immunohistochemistry before and after treatment. H. pylori was not eradicated and patients were followed for an average of 6.6 years (range 3-14.1 years). In addition to immunohistochemistry, anti-H(+), K(+)-ATPase reactivity was assessed by Western blot in paired sera of 41 patients (26 H. pylori-positive and 15 uninfected) and results are critically evaluated. RESULTS: In immunohistochemistry, all patients were negative for anti-canalicular autoantibodies when omeprazole therapy started, except for two patients with corpus-predominant gastritis in the presence of H. pylori. One patient, who was H. pylori-negative, newly developed an anti-canalicular antibody response during therapy. CONCLUSIONS: Our results indicate that, as compared with non-infected patients, long-term profound acid suppression therapy in H. pylori-infected gastro-oesophageal reflux disease patients does not increase or accelerate gastric autoimmunity.

Association between infection with Helicobacter pylori and Chlamydia pneumoniae and risk of ischemic stroke subtypes: Results from a population-based case-control study.

BACKGROUND AND PURPOSE: Helicobacter pylori and Chlamydia pneumoniae have been associated epidemiologically and pathogenetically with coronary atherosclerosis. However, population-based data on chronic infection and stroke are lacking. Therefore, we investigated the association of both bacterial pathogens and ischemic stroke subtypes in a population-based case-control study. METHODS: Patients with first ischemic stroke in the population-based Erlangen Stroke Project were collected as cases. Neighborhood controls were drawn from the study population, matched for age, sex, and place of residence. IgG antibodies to H pylori were measured by enzyme immunoassay, and IgG antibodies to C pneumoniae were measured by microimmunofluorescence technique. Conditional logistic regression was used. Analyses were stratified for etiologic stroke subtypes according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. RESULTS: A total of 145 case and 260 control subjects were included. Chronic H pylori infection was associated with a higher risk of stroke caused by small-artery occlusion (adjusted odds ratio, 3.31; 95% CI, 1.15 to 9.56) and a lower risk of cardioembolic stroke (adjusted odds ratio, 0.21; 95% CI, 0.06 to 0.71). Overall, elevated H pylori as well as elevated C pneumoniae antibodies were not associated with ischemic stroke. CONCLUSIONS: Our population-based study does not provide evidence of any strong association between the immune response to C pneumoniae as a marker of prior infection and ischemic stroke. Further studies are required to reveal the role of chronic H pylori infection as an independent risk factor for the subgroup small-artery occlusion.

Evidence of novel pathogenic pathways for the formation of antigastric autoantibodies in Helicobacter pylori gastritis.

Autoantibodies against gastric epithelial cells are detectable in up to 50% of patients with chronic, active Helicobacter pylori gastritis. Presence of autoantibodies against canalicular structures within human parietal cells (anticanalicular autoantibodies) correlate with gastric mucosa atrophy. It has been suggested, that molecular mimicry between H pylori and the host on the level of Lewis X and Lewis Y blood group antigens leads to these autoantibodies. This study aimed at analysing whether antigastric antibodies can be absorbed to Lewis X or Y positive H pylori strains. Sera from 14 H pylori infected patients with anticanalicular autoantibodies were effectively absorbed to H pylori. Immunohistochemical studies of the absorbed sera showed no decrease of antigastric autoreactivity. Pathogenic mechanisms other than molecular mimicry lead to the formation of antigastric autoantibodies, and epitopes other than Lewis antigens are the autoimmune targets.

Late pulmonary metastasis in uterine PEComa.

Perivascular epithelioid cell tumours (PEComas) other than angiomyolipoma, clear cell "sugar" tumour of the lung, and lymphangioleiomyomatosis are very rare mesenchymal tumours. The uterus seems to be the most prevalent site of involvement, but only 13 cases of uterine PEComa have been described. Three of these cases exhibited local aggressive behaviour and only one showed metastasis. Because of the extremely small number of cases, PEComas are considered tumours of uncertain malignant potential. This report describes a 68 year old woman, who presented with multiple pulmonary lesions seven years after the initial diagnosis of well differentiated endometrial stromal sarcoma. Histological and immunohistochemical analysis of the pulmonary lesions, in addition to re-evaluation of the primary uterine tumour, led to the final diagnosis of metastatic uterine PEComa. The findings indicate that any PEComa might have malignant potential. Spreading of this tumour to other organs might become evident even several years after primary manifestation.

Antigastric autoantibodies in Helicobacter pylori gastritis: prevalence, in-situ binding sites and clues for clinical relevance.

Colonization of human gastric mucosa with Helicobacter pylori leads to chronic active gastritis and induces the occurrence of an acquired mucosa-associated lymphoid tissue (MALT) in the stomach. This remodelling of the gastric mucosa together with chronic antigen persistence may induce autoimmune reactions. The aim of this study was to investigate humoral autoimmune reactions to human gastric mucosa in H. pylori gastritis and their clinical relevance. Sera from patients with dyspeptic symptoms were tested for presence of IgG immunoglobulins against H. pylori. Gastric infection with H. pylori and alterations of gastric mucosa were demonstrated by histological examination of gastric biopsy specimens. All sera were tested for reactivity against human gastric mucosa by immunohistochemistry. Two different in-situ binding sites of antigastric autoantibodies were observed. Binding to canalicular structures within parietal cells was significantly correlated with antibodies to H. pylori, elevated basal gastrin levels and atrophy of gastric corpus glands. Our data indicate that autoimmune reactions to antigens in the human gastric mucosa occur in H. pylori gastritis and that they may play a role in the pathogenesis of the disease.

Significant increase in antigastric autoantibodies in a long-term follow-up study of H. pylori gastritis.

In 30% of H. pylori-infected patients a certain type of antigastric autoantibodies, reacting against canalicular structures within human parietal cells, is detectable. Furthermore, it has been shown that these autoantibodies are correlated with atrophy of the mucosa in the corpus. The aim of this study was to analyse the prevalence of these anticanalicular autoantibodies (ACAB) and their significance for development of gastric mucosa atrophy in a 12-year follow-up period. Gastric biopsy specimens from 62 persons in Saaremaa Island, Estonia, were collected in 1997 and assessed independently by two pathologists in accordance with the updated Sydney system. The sera of these persons were immunohistochemically screened for ACAB and for classic parietal cell antibodies (PCA). In addition, for 37 of the 62 persons, gastric biopsies and sera collected 12 years earlier (1985) were investigated in an analogous manner. ACAB increased significantly, from 8 out of 37 in 1985 to 17 out of 37 in 1997 (P=0.004; McNemar test). In 1997 a significant correlation existed between the presence of ACAB and corpus mucosa atrophy (19 out of 30 versus 10 out of 32 without atrophy; P=0.01; odds ratio (OR)=3.8, 95% CI 1.4-10.6). However, no correlation was found between ACAB and development of atrophy in the period from 1985 to 1997. All 37 persons were PCA negative in 1985, whereas in 1997, 2 turned out to be PCA positive. ACAB increased significantly with duration of H. pylori gastritis. The correlation between ACAB and presence of gastric corpus atrophy was confirmed. However, it is possible that ACAB are the consequence of and not a causative factor in gastric mucosa atrophy, insofar as the association of ACAB with progression of corpus atrophy was not significant.

Apoptosis in chronic gastritis and its correlation with antigastric autoantibodies.

In the course of time, chronic gastritis may result in gastric atrophy, as in type A gastritis, where autoimmune reactions against parietal cells result in a loss of corpus glands. Two antigastric autoantibodies have been detected in Helicobacter pylori gastritis and are described as anti-luminal and anti-canalicular autoantibodies. The aim of this study was to determine whether increased apoptosis may be responsible for the loss of gastric epithelium and whether this apoptosis is correlated with antigastric autoimmunity. Gastric biopsies from normal mucosa and Helicobacter pylori gastritis were analysed for the presence of apoptosis using the TUNEL method. Helicobacter pylori gastritis was divided into cases (1) without autoantibodies, (2) with anti-luminal, and (3) with anti-canalicular autoantibodies. Apoptotic cells of the foveolar and of the glandular epithelium in the antrum and corpus were counted. The number of apoptotic cells in the gastric mucosa was significantly increased in all cases of gastritis. The highest number of apoptotic cells was observed in the gastric glands of the corpus mucosa in Helicobacter pylori gastritis with anti-canalicular autoantibodies. Apoptosis contributes to the development of gastric atrophy and there are various types of Helicobacter pylori gastritis. The positive correlation between apoptotic cell loss in the glandular zone of the corpus mucosa and the presence of anti-canalicular autoantibodies indicates a possible link between anti-gastric autoimmunity and atrophy in this type of Helicobacter pylori gastritis--similar to that in classic type A gastritis.

Histopathological diagnosis of Barrett's mucosa and associated neoplasias: results of a consensus conference of the Working Group for Gastroenterological Pathology of the German Society for Pathology on 22 September 2001 in Erlangen.

There are a number of difficulties regarding the diagnosis of Barrett's mucosa and the varying grades of neoplasia that may be associated with it. It was, therefore, the aim of a consensus conference of the Working Group for Gastroenterological Pathology within the German Society of Pathology to achieve standardisation regarding the following issues: definition and diagnostic criteria for Barrett's mucosa and its discrimination from intestinal metaplasia of the cardia, diagnostic criteria for intraepithelial neoplasia, number of biopsies necessary to establish the diagnosis, significance of additional immunohistochemical and/or molecular methods as well as importance of a second opinion in the diagnosis of intraepithelial neoplasia.

Role of antigastric autoantibodies in chronic Helicobacter pylori infection.

In recent studies a significant association between H. pylori infection and antigastric autoimmunity has been reported. Antigastric autoantibodies can be found in more than 30% of infected patients. Two distinct binding patterns of these autoantibodies have been described, first at the luminal membrane of the foveolar epithelium, and second at the canaliculi membranes of the parietal cells in the body mucosa. The latter type of autoantibodies correlates with histologic and clinical parameters of gastric mucosa atrophy. The gastric H,K-ATPase, which is known to be the autoimmune target in classical autoimmune gastritis, also represents a major autoantigen in atrophic H. pylori gastritis. Molecular mimicry between H. pylori and the host does not seem to be responsible for the generation of this type of autoreactivity. The development of antigastric autoantibodies may be a relevant host factor which contributes to the final clinical outcome of chronic H. pylori gastritis.