Rethinking the relationship between flood risk perception and flood management.

Although flood risk perceptions and their concomitant motivations for behaviour have long been recognised as significant features of community resilience in the face of flooding events, there has, for some time now, been a poorly appreciated fissure in the accompanying literature. Specifically, rationalist and constructivist paradigms in the broader domain of risk perception provide different (though not always conflicting) contexts for interpreting evidence and developing theory. This contribution reviews the major constructs that have been applied to understanding flood risk perceptions and contextualises these within broader conceptual developments around risk perception theory and contemporary thinking around flood risk management. We argue that there is a need to re-examine and re-invigorate flood risk perception research, in a manner that is comprehensively underpinned by more constructivist thinking around flood risk management as well as by developments in broader risk perception research. We draw attention to an historical over-emphasis on the cognitive perceptions of those at risk to the detriment of a richer understanding of a wider range of flood risk perceptions such as those of policy-makers or of tax-payers who live outside flood affected areas as well as the linkages between these perspectives and protective measures such as state-supported flood insurance schemes. Conclusions challenge existing understandings of the relationship between risk perception and flood management, particularly where the latter relates to communication strategies and the extent to which those at risk from flooding feel responsible for taking protective actions.

[Bronchoscopic resection of an endobronchial hamartochondroma]. / Bronchologische Therapie eines endobronchialen Hamartochondroms.

The endobronchial hamartochondroma is a very rare, slowly growing benign tumor. We report a case of hamartochondroma conglomerate located in the left main bronchus. The resection via rigid endoscopy with ND-YAG laser and forceps was successful, and no complications occured. The rigid endoscopy with laser-application in such case is a safe and effective procedure in endobronchial hamartochondroma.

Immune response to autologous and heterologous Helicobacter pylori antigens in humans.

Infection of humans with Helicobacter pylori results in the development of chronic gastritis and plays an important role in gastric ulcer pathogenesis. Despite the infiltration of the mucosa with specific immunocompetent cells and production of specific antibodies, the infection usually persists for life. This study was performed to investigate if immunologic mechanisms exist which could contribute to the inability of the host to terminate the infection. Therefore, we compared the in vitro immunoreactivity of peripheral blood mononuclear cells (PBMC) from H. pylori-infected patients after stimulation with sonicated H. pylori bacteria from the stomach of the patient (autologous bacterial strain) with stimulation by bacteria from other patients (heterologous bacteria). We measured cell proliferation, expression of T cell activation markers CD25, HLA-DR, and CD71, as well as production ofinterleukin-10 (IL-10), an inhibitory cytokine. We found that the proliferative response of PBMC was significantly lower after autologous than after heterologous stimulation. Furthermore, secretion of IL-10 in the culture supernatants was significantly higher when PBMC were incubated with autologous than with heterologous H. pylori antigens. No significant differences between autologous or heterologous stimulation were observed in the increased expression of T cell activation markers. These data indicate that systemic immunologic response to H. pylori are strain-dependent. For further studies of the immune responses towards H. pylori, the use of an autologous stimulatory system seems necessary.

Decreased Helicobacter pylori-specific gastric secretory IgA antibodies in infected patients.

Despite an increase in local Helicobacter pylori-specific IgA production in H. pylori infection, the bacterium is able to persist over decades. We focused on IgA and secretory IgA (sIgA) in gastric juice because sIgA is more relevant in local protection and more resistant to degradation than nonsecretory IgA. H. pylori-specific IgA and sIgA in gastric juice, saliva, and serum of H. pylori-infected patients were compared. Samples from 28 H. pylori-positive and 16 negative patients were tested by means of immunoblotting for the presence of H. pylori-specific IgA and sIgA. In gastric juice the majority of H. pylori-specific IgA was not of the secretory type, whereas total IgA was bound mainly to the secretory component as shown by immunoblot and slot blot. In contrast H. pylori-specific IgA antibodies in saliva of infected patients were of the secretory type as shown by immunoblot. The presence of specific, nonsecretory IgA may be a consequence of the damaged mucosal epithelium at the site of H. pylori infection allowing IgA to bypass the secretory transport system. Considering the resistance of secretory IgA against hydrolysis and proteolysis, these data suggest that the predominantly nonsecretory IgA specific for H. pylori may lead to a decreased protection against H. pylori.

Partial characterization of a cell proliferation-inhibiting protein produced by Helicobacter pylori.

Despite the induction of an immunological reaction, Helicobacter pylori-associated gastritis is a chronic disease, suggesting that this microbe can evade the host immune defense. Previous studies by our group showed that H. pylori suppresses the in vitro proliferative response of human mononuclear cells to mitogens and antigens. Here we demonstrate that the antiproliferative activity of H. pylori also affects the proliferation of various mammalian cell lines (U937, Jurkat, AGS, Kato-3, HEP-2, and P388D1). This effect is detectable in the first 16 h of incubation and maximal between 24 and 48 h. In addition, the presence of H. pylori significantly diminished the protein synthesis of cells in the first 6 h of incubation, comparable to the results with cycloheximide and diphtheria toxin. The urease enzyme, the cagA gene product, and the vacuolizing cytotoxin of H. pylori were excluded as causative agents of the antiproliferative effect by using isogenic knockout mutant strains. The inhibitory effect was not due to a lytic activity of this bacterium. The results reported here indicate that the responsible factor is a protein with an apparent native molecular mass of 100 +/- 10 kDa. Our work implicates the presence of a protein factor in H. pylori (termed PIP [for proliferation-inhibiting protein]) with antiproliferative activity for mammalian cells, including immunocompetent and epithelial cells. Thus, it is reasonable to presume that this property may contribute to the pathogenesis of H. pylori-induced diseases. It may be involved on the one hand in immune response evasion and on the other hand in the suppression of epithelial repair mechanisms.

Early mobilization following carpal tunnel release. A prospective randomized study.

A prospective randomized study was undertaken of 50 consecutive patients undergoing surgery for idiopathic carpal tunnel syndrome to determine the value of splintage of the wrist following open carpal tunnel release. Patients were randomized to either be splinted for 2 weeks following surgery or to begin range-of-motion exercises on the first post-operative day. Subjects were evaluated at 2 weeks, 1 month, 3 months, and 6 months after surgery by motor and sensory testing, physical examination, and a questionnaire. Variables assessed included date of return to activities of daily living, dates of return to work at light duty and at full duty, pain level, grip strength, key pinch strength, and occurrence of complications. Patients who were splinted had significant delays in return to activities of daily living, return to work at light and full duty, and in recovery of grip and key pinch strength. Patients with splinted wrists experienced increased pain and scar tenderness in the first month after surgery; otherwise there was no difference between the groups in the incidence of complications. We conclude that splinting the wrist following open release of the flexor retinaculum is largely detrimental, although it may have a role in preventing the rare but significant complications of bowstringing of the tendons or entrapment of the median nerve in scar tissue. We recommend a home physiotherapy programme in which the wrist and fingers are exercised separately to avoid simultaneous finger and wrist flexion, which is the position most prone to cause bowstringing.

Neutrophil activation by Helicobacter pylori lipopolysaccharides.

Helicobacter pylori-induced release of toxic substances by neutrophils could be of potential importance in the pathogenesis of gastroduodenal inflammatory diseases. Lipopolysaccharide (LPS) has the ability to induce neutrophil activation at very low concentrations. Neutrophil oxidative metabolism and enzyme release were assessed after stimulation of neutrophils with various preparations of LPS from H. pylori and compared with that obtained with Salmonella typhimurium LPS. No direct activation of neutrophils by LPS was observed. Preincubation with LPS showed a significant priming for increased activity on subsequent stimulation, particularly with rough-form LPS. The potency of H. pylori LPS was 10-fold lower than that of S. typhimurium LPS, probably reflecting the unique biochemical structure of H. pylori LPS. Chronic low-grade stimulation by H. pylori LPS in the gastric mucosa may render neutrophils primed for the excessive release of detrimental substances into the tissue on stimulation by other mediators.

Fumarate reductase of Helicobacter pylori--an immunogenic protein.

An immunogenic protein with an apparent mol. wt of 80 kDa that was recognised by 55% of sera from patients infected with Helicobacter pylori in Western blots was found in butanol extracts of H. pylori membranes. The N-terminal amino-acid sequence of the 80-kDa protein showed 80% identity with the N-terminal sequence of subunit A of the fumarate reductase of Wolinella succinogenes, suggesting the existence of a fumarate reductase in H. pylori. The membrane fraction of H. pylori catalysed succinate oxidation with methylene blue at a specific enzyme activity of 0.06 U/mg of protein. The enzyme was purified by Triton X100 extraction followed by ion-exchange chromatography. The purified enzyme contained an 80-kDa protein which was recognised by rabbit serum raised against subunit A of fumarate reductase of W. succinogenes. A second protein band with a mol. wt of 31 kDa was recognised by rabbit serum raised against subunit B of fumarate reductase of W. succinogenes. Two-dimensional gel electrophoresis demonstrated that the 80- and 31-kDa proteins were subunits of one protein complex. These results indicate that H. pylori contains an enzyme that is very similar to W. succinogenes fumarate reductase. The 80-kDa subunit was recognised in sonicates of all 32 H. pylori strains tested by rabbit antibodies raised against subunit A of fumarate reductase of W. succinogenes, indicating that fumarate reductase is a common protein in H. pylori. The fumarate reductase of H. pylori might enable the bacterium to perform anaerobic respiration in a similar fashion to other anaerobic or facultative bacteria.

Suppression of human mononuclear cell response by Helicobacter pylori: effects on isolated monocytes and lymphocytes.

Helicobacter pylori colonization of the human gastric mucosa causes a long-term, not self-limiting inflammation, suggesting that the microbe has properties to protect itself against the host immune defence system. Recently we were able to demonstrate that H. pylori suppresses the in vitro proliferative response of human peripheral blood mononuclear cells to antigens as well as to mitogens without affecting cell viability. The purpose of this study was to clarify which cell subsets of mononuclear cells are influenced by H. pylori. The use of monocytes which had been pretreated with a soluble cytoplasmic fraction of H. pylori (30 micrograms ml-1) led to a suppressed proliferation of T cells after PHA-activation. Activation of isolated T cells with PHA and PMA revealed that the proliferative response of lymphocytes could also be inhibited independently of monocytes. The anti-proliferative effect was associated with a reduction of IL-2 receptor (CD25) expression as well as an inhibition of blastogenesis. Furthermore, the spontaneous proliferation of EBV-transformed B cell lines was suppressed in a dose-dependent manner. FACS-analysis of HLA-DR, ICAM-1 and CD14 expression on the surface of monocytes revealed an influence of H. pylori on CD14 expression at a concentration of 30 micrograms ml-1, while the expression of HLA-DR and ICAM-1 was not affected at this concentration.

Stimulatory effects of Helicobacter pylori on human peripheral blood mononuclear cells of H. pylori infected patients and healthy blood donors.

The ability of 23 different strains of Helicobacter pylori to induce proliferative response of human peripheral blood mononuclear cells (PBMC) was investigated. All tested strains stimulated the DNA synthesis of PBMC from both healthy and H. pylori infected blood donors, but with lower stimulation of PBMC of infected donors. Using different bacterial antigen preparations, such as crude membranes, cytoplasmic proteins, and urease, a significantly lower induction of the proliferative response of PBMC from H. pylori infected than from healthy blood donors could also be demonstrated. In contrast to this result the reaction to phytohemagglutinin and purified protein derivative of tuberculin was similar in both groups. The stimulation pathway was interleukin 2 (IL-2) dependent as proved by inhibition of the proliferative response with an alpha-IL-2-receptor antibody. Using an antibody against HLA-DR the lymphoproliferation could also be blocked showing the importance of the major histocompatibility class II (MHCII) complex. Only coincubation of T cells with monocytes plus antigen or with antigen-preincubated monocytes led to a proliferative response showing the necessity of antigen-presenting cells. At least a part of the lymphoproliferative response is MHCII restricted as could be shown with H. pylori specific T-cell lines. These results and the kinetics of the proliferative response with a maximum at day 7 suggest that the proliferative response of human PBMC was mainly induced by antigens than by a mitogen.

Immune suppressive effects of Helicobacter pylori on human peripheral blood mononuclear cells.

Helicobacter pylori, the causative agent of type-B gastritis and duodenal ulcer in man is described as a bacterium able to stimulate the human immune system. This study demonstrates that H. pylori besides this property possesses an immune suppressive activity. The in vitro proliferation of human peripheral blood mononuclear cells to purified protein derivative of tuberculin (PPD), phytohemagglutinin, and concanavalin A was reduced in a dose-dependent manner by bacteria which had been inactivated by incubation at 56 degrees C as well as by a soluble cytoplasmic fraction of H. pylori. The immune suppressive effect on the mitogen-induced proliferation could be increased by preincubation of the mononuclear cells with H. pylori. The observed effect does not seem to be a specific phenomenon depending on prior exposure of the blood donors to H. pylori, since suppression occurred with mononuclear cells of H. pylori-infected patients as well as of antibody-negative healthy control individuals. The suppressive activity was non-dialyzable, heat-labile (100 degrees C, 30 min) and sensitive to trypsin. Furthermore, the treatment at 100 degrees C caused an increase in the capability of H. pylori to induce lymphoproliferation. This fact indicates that the suppressive factor is also effective on H. pylori antigens. While exogenous interleukin-2, could to a certain extent, restore the responsiveness of the lymphocytes after PPD-stimulation in the presence of H. pylori, the addition of interleukin-1 had no effect on the suppressed lymphoproliferation. Cell-separation and cell-mixing experiments indicated that an influence on monocytes rather than on T cells is the major cause of the observed suppressive effect. Although the immunological mechanisms involved in H. pylori-associated gastritis are not clearly defined, it is reasonable to presume that suppression of host defense mechanisms may contribute to the pathogenesis of this disease.

Immunological activity of lipopolysaccharide of Helicobacter pylori on human peripheral mononuclear blood cells in comparison to lipopolysaccharides of other intestinal bacteria.

Lipopolysaccharide of Helicobacter pylori was tested for its mitogenicity and for its ability to stimulate cytokine release in human peripheral blood mononuclear cells (PBMC) of healthy and H. pylori-infected blood donors. Mitogenicity in PBMC induced by H. pylori LPS was similar to that induced by Campylobacter jejuni lipopolysaccharide, but lower than that induced by Escherichia coli lipopolysaccharide in the H. pylori negative blood donor group. Furthermore, H. pylori LPS was able to induce tumour necrosis factor (TNF) interleukin 1 (IL-1) and interleukin 6 (IL-6) secretion of PBMC. Compared with the ability of C. jejuni and E. coli lipopolysaccharides to stimulate cytokine release, H. pylori lipopolysaccharide induced a significantly lower TNF and IL-1 secretion of PBMC than the other tested bacterial lipopolysaccharides. Similar amounts of IL-6 release were obtained by stimulation of PBMC with H. pylori and C. jejuni lipopolysaccharides, whereas a higher IL-6 release was measured by stimulation with E. coli lipopolysaccharide. The results of this study suggest that H. pylori lipopolysaccharide has a lower immunological activity than lipopolysaccharides of other intestinal bacteria. This is probably due to its unusual acylation and phosphorylation pattern of lipid A.

[Modified combined omeprazole/amoxicillin therapy for Helicobacter pylori eradication: a pilot study]. / Modifizierte kombinierte Omeprazol/Amoxicillin-Therapie zur Helicobacter-pylori-Eradikation: eine Pilotstudie.

Patients with H.pylori positive peptic ulcer disease were treated with a two weeks regimen consisting of 20 mg omeprazole twice daily and 500 mg amoxicillin six times daily. Subsequently, an H2-receptor antagonist was started (300 mg ranitidine) at night time for four weeks. Before and one month after completion of antibiotic therapy an upper GI-tract endoscopy was performed for determination of H.pylori infection [biopsy urease test (BUT), specific culture and histologic demonstration]. A total of 12 patients completed the study protocol. H.pylori eradication, defined as a negative result in BUT, culture and histology) four weeks after completion of the combined omeprazole/amoxicillin treatment regimen was achieved in 91.6% (11 of 12 patients). Complete ulcer healing was confirmed in all patients. A stomatitis was observed in one female patient as a possible side effect of antibiotic treatment, but this did not necessitate discontinuation of therapy. Only complicated drug regimen with many side effects have been available so far for successful eradication of H.pylori. Thus, the present drug combination might prove as an effective therapeutic option in the future. These data, however, await confirmation in larger study population.

Intermediate filaments vimentin and desmin share epitopes with M 1 protein of group A streptococci.

The cross reactivity of the murine monoclonal antibody PM II 40 against human glomeruli with streptococcal type 1 M protein was investigated. The antibody PM II 40 recognized a protective epitope on a glomerulonephritis-associated M type 1 strain. A 23 kD streptococcal surface protein extracted by limited pepsin digestion reacted with PM II 40 in the Western immunoblot. The aminoterminal sequence of this peptide was identical to the known aminoterminal amino acid sequence of type 1 M protein. Human renal podocytes carry the cross-reactive antigen of the antibody PM II 40 as could be shown by electron microscopy. The podocytes cultured from isolated human glomeruli showed a fibrillar pattern with the antibody in the immunofluorescence test. An anti-vimentin antibody and the antibody PM II 40 recognized the same proteins with molecular weights of 54, 52 and 43 kD of SDS-extracted isolated human glomeruli suggesting that vimentin is the glomerular antigen. The antibody PM II 40 not only react with vimentin but also with desmin suggesting that the recognized epitopes are distinct from that described by Kraus et al. for vimentin and type 1 M protein.

[Pathogenesis of glomerulonephritis following streptococcal infection]. / Die Pathogenese der Glomerulonephritis nach Streptokokkeninfektion.

Group A streptococci are responsible for the induction of serious pyoderma and pharyngitis in humans. The nonsuppurative sequelae "acute rheumatic fever" (ARF) and "acute poststreptococcal glomerulonephritis" (APGN) do very often occur with variable attack rates in epidemics with these microorganisms. At present, immune complex formation in the blood circulation system, in situ complex formation within the glomeruli, antibody cross-reactions between beta-hemolytic group A streptococci and human kidney tissue as well as tissue damage independent of specific antibodies are intensively discussed to explain the pathogenesis of acute poststreptococcal glomerulonephritis. However, the pathophysiological course of APGN has not yet been precisely identified.