Search

Eine Immunsuppression muss bei vielen Patienten in Kauf genommen werden – gleich ob bei der Behandlung von Autoimmun- oder rheumatischen Erkrankungen therapeutisch erwunscht oder als Nebeneffekt bei der Verhinderung der Transplantatabstosung oder bei der Behandlung von malignen Erkrankungen. Damit konnen jedoch Infektionen mit zum Teil seltenen, opportunistischen Erregern oder in einer durch den Immundefekt atypischen Prasentation verbunden sein, die diagnostische oder therapeutische Probleme bereiten. In dieser Ubersicht sollen daher bei nicht-neutropenischen Immunsupprimierten typischerweise auftretende Infektionen vorgestellt und Hinweise zu deren Diagnostik, Prophylaxe und Therapie gegeben werden.

It is believed that an inflammation-induced activation of the CNS leads to an inhibition of overshooting immune responses to prevent extensive local cytokine secretion. However, immunosuppression by the sympathetic nervous system may be unfavorable when bacteria are present locally and when TNF-α is necessary to overcome infection. We now report in a superfusion model, using mouse spleen slices, that although local Pseudomonas aeruginosa increased splenic TNF-α and IL-6 secretion severalfold over basal levels, electrically released neurotransmitters attenuated cytokine secretion to similar basal level as under bacteria-free conditions. Bacteria reversed noradrenergic inhibitory effector mechanisms: Under bacteria-free conditions, TNF-α secretion was very low and IL-6 secretion was mainly inhibited by α2-adrenoreceptor ligation. In the presence of bacteria, TNF-α and IL-6 secretion were high and IL-6 secretion was mainly inhibited by β-adrenoreceptor ligation. The α- to β-adrenoswitch of IL-6 inhibition in...

Background Lipopolysaccharides (LPSs) are thought to be one of the triggers of organ reactions to sepsis, which causes hepatocellular dysfunction. This dysfunction can be demonstrated by a reduction of organic anion transport The aim of our study was to assess whether the transport of indocyanine green (ICG) is affected by LPS, and whether Kupffer cells are involved. Methods Single-pass liver perfusion with ICG at a concentration of 57.8 mg/kg/min was performed for 130 min. pH, oxygen tension and perfusion pressure were continuously measured in influent and effluent. Taurocholate was infused at 48.3 mg/kg/min to achieve a stable bile flow. LPS was added at concentrations of 0.45, 0.9 and 1.44 mg/kg/min for 30 min. ICG was determined photometrically in perfusate and bile. To depress the function of Kupffer cells male Wistar rats were treated with GdCl 3 24 h in advance. Primary cultured hepatocytes were used for studying the direct effect of LPS on the uptake rate of ICG. Results Forty-five minutes after administration of LPS a significant dose-dependent decrease of ICG uptake was seen in animals treated with LPS. Livers of animals pretreated with GdCl 3 did not show this decrease. LPS had no direct effect on the uptake of ICG into primary cultured hepatocytes, whereas treatment of these cells with 8-bromo-cGMP resulted in a significant increase of ICG uptake. Conclusion LPS has a rapid dose-dependent effect on the detoxification properties of the liver for ICG. The rapid effect of LPS on ICG uptake in hepatocytes is mediated by Kupffer cells.

Die vorliegende Ubersicht befast sich nicht nur mit der bildgebenden Diagnostik dieser Erkrankungen, sondern ausfuhrlich mit Epidemiologie, Atiologie, Pathogenese, Verlauf und Therapie der Colitis ulcerosa und des M. Crohn, da diese Aspekte wesentlich zum Verstandnis fur die Fragestellungen an bildgebende Verfahren und die sich daraus ergebenden therapeutischen Konsequenzen beitragen.

There is increasing evidence that the intestinal microflora plays an important role in the pathogenesis of inflammatory bowel disease. In the present study, we examined the role of the resident intestinal flora in our model of dextran sulfate sodium (DSS)-induced acute and chronic colitis in mice.Acute colitis was induced in BALB/c mice with 5% DSS in their drinking water for 7 days. Chronic colitis was established after four cycles of feeding 5% DSS for 7 days and water for 10 days. For eliminating intestinal bacteria, mice were injected intraperitoneally with metronidazole and ciprofloxacin. We analysed four parameters: (1) body weight, (2) length of the colon, (3) histological score, and (4) myeloperoxidase activity.In acute DSS colitis treatment with antibiotics led to an improvement of the histological parameters (epithelial damage, P0.05; inflammatory infiltrate, P0.05) and colon length (P0.0028). A significant reduction in granulocyte infiltration was indicated by a 52.6% reduced myeloperoxidase activity in colonic biopsies. By contrast, in chronic colitis, treatment of mice with antibiotics failed to show significant effects.In acute DSS-induced colitis bacteria and/or bacterial products play a major role in initiation of inflammation but not in chronic DSS colitis.

□ Hintergrund Auch bei grampositiven Erregern wurden in den letzten Jahren vermehrt Antibiotikaresistenzen beobachtet. Fur die Glykopeptidantibiotika (zum Beispiel Vancomycin) ist die Resistenzsituation noch relativ gunstig. Internationale Richtlinien empfehlen, den Einsatz von Glykopeptiden auf das unbedingt notwendige Mas zu beschranken, um eine Resistenzentwicklung fur diese Substanzgruppe zu vermeiden. In Landern, in denen Antibiotikarestriktionen verbreitet Anwendung finden, uben die Klinikapotheken in der Regel diese Kontrollfunktion aus. An deutschen Krankenhausern gestaltet sich eine entsprechende Uberwachung der Antibiotikaverschreibungspraxis jedoch schwieriger, da durch die dezentrale Medikamentenbevorratung auf den Stationen die Uberprufung der Indikation einer individuellen Antibiotikaverordnung durch eine zentrale Stelle in der Regel nicht moglich ist.

Die rheumatoide Arthritis ist eine chronische systemische Erkrankung bislang ungeklarter Atiologie, bei det es in den betroffenen Gelenken zu entzundlichen Veranderungen, synovialer Hyperplasie und einer Destruktion des angrenzenden Knorpel- und Knochengerustes kommt. Mit neu entwickelten molekularbiologischen Methoden konnten in den letzten Jahren wichtige zullulare und molekulare Ablaufe in der Pathogenese der rheumatoiden Arthritis aufgeklart werden. Eines der Schlusselereignisse in der Pathogenese der rheumatoiden Arthritis ist die zellulare Aktivierung aggressiv wachsender, matrixabbauender synovialer Fibroblasten. Diese zellulare Aktivierung ist unter anderem durch eine veranderte Expression apoptoseregulierender Molekule (zum Beispiel CD 95 und Sentrin) und von Protoonkogenen (zum Beispiel RAS und MYC) gekennzeichnet. Wichtige externe Stimuli sind proinflammatorische Zytokine, die bei der rheumatoiden Arthritis in einem unausgewogenen Verhaltnis synthetisiert werden. Erste therapeutische Studien mit zytokinhemmenden Molekulen (Interleukin-1-Rezeptor-Antagonist, rekombinanter loslicher TNF-α-Rezeptor/Etanercept und monoklonale TNF-α Antikorper/Remicade) zeigten vielversprechende Ergebnisse. Etanercept ist seit kurzem in den USA zur Therapie der rheumatoiden Arthritis zugelassen. Das pharmakokinetische Problem einer kontinuierlichen Expression der therapeutischen Molekule im Gelenk konnte durch Gentransfermethoden gelost werden; auch hier ist eine erste Studie mit dem Interleukin-1-Rezeptor-Antagonisten durchgefuhrt worden. Die gelenkdestruktiven Effekte der aktivierten synovialen Fibroblasten werden uber matrixabbauende Enzyme, wie die Familie der Matrixmetalloproteasen, vermittelt, deren Beeinflussung ein weiteres therapeutisches Prinzip darstellen konnte. Die Aufklarung pathophysiologisch wichtiger Stoffwechselwege in der rheumatoiden Arthritis hat zu neuen Ansatzen in der Therapie der Erkrankung gefuhrt. Gentransfermethoden sind fur die Erforschung der Pathophysiologie der rheumatoiden Arthritis von groser Bedeutung, die Moglichkeit und Sicherheit eines klinischen Einsatzes sind aber noch durch weitere Studien zu belegen.

Objective The prevalence of anti-HCV in Germany has been determined for blood donors and certain risk groups, but the burden of disease in the general population remains unknown. The aim of this study was to determine the prevalence of anti-HCV in a study group representing the normal adult German population. Design A total of 5312 individuals aged 18-70 years were randomly selected from small, middle-sized and big cities in five different German states. Sera were tested for anti-HCV by enzyme immunoassay and immuno dot assay, as well as for anti-HBc and, in the case of a positive result, for anti-HBs and HBsAg. Serological typing was performed in anti-HCV-positive persons. Results Thirty-nine individuals were anti-HCV positive; indeterminate results (with antibodies against the viral core protein only) were obtained in 20. There was a tendency to higher prevalence rates with increasing age as well as to a higher prevalence in women. Serological typing revealed the presence of genotype 1 in the vast majority of participants (82%); only a minority showed genotype 3 (7.2%) or other genotypes (7.2%). Markers of HBV were seen in 43.6% of the anti-HCV positive individuals, with nearly one third (29.4%) of the double-infected showing anti-HBc as the only marker for HBV. Conclusions According to our data, an anti-HCV prevalence of 0.63% (95% confidence interval, CI, 0.42-0.84%) can be assumed in the general adult German population, with higher values in older people and women. Nearly half of the anti-HCV positive individuals also show markers of hepatitis B virus.

Background and aims Macrophages play an important role during mucosal inflammation in inflammatory bowel disease (IBD). As the co-stimulatory molecules B7-1 (CD80) and B7-2 (CD86) play an integral role in the activation of T cells by antigen-presenting cells (APC) we investigated the surface expression of B7-1 and B7-2 on colonic macrophages from normal and IBD mucosa. Methods Intestinal macrophages were isolated from biopsies of 13 control persons and 14 patients with IBD (seven with Crohn's disease (CD); and seven with ulcerative colitis (UC)). Cells were characterized by triple fluorescence flow cytometrical analysis using CD33 as macrophage marker. Results The expression of B7-1 (CD80) (9.2% +/- 4.2%) and B7-2 (CD86) (15.1% +/- 7.3%) was low on colonic macrophages from normal mucosa, indicating only a low antigen presenting potential. However, on macrophages from IBD colon there was a significant increase in the expression of co-stimulatory molecules (CD80, 33.8% +/- 8.9%, P = 0.00005 vs. control; CD86, 39.9% +/- 8.8%, P = 0.00002). There was no significant difference between CD and UC in the expression of CD80 (CD, 31.3% +/- 6.7%; UC, 34.4% +/- 13.3%) and CD86 (CD, 41.9% +/- 3.8%; UC, 35.6% +/- 13.8%). While in normal mucosa only 10.6% +/- 4.9% of the macrophages expressed CD14, more than 90% of the CD86/CD80 positive cells of the inflamed mucosa were positive for CD14. Conclusion Colonic macrophages from normal mucosa rarely express the co-stimulatory molecules CD80 and CD86. In IBD a new macrophage population is found with high expression of co-stimulatory molecules presumably responsible for the perpetuated immune response.

Human B cell hybridomas were established to define new autoantigens of importance for autoimmune diseases such as rheumatoid arthritis (RA). One lgG1, lambda monoclonal antibody (FKN-E12), was derived from synovial B lymphocytes of a patient with sero-negative RA. The purified lg was used to select specifically binding peptides from a random peptide phage display library. Only one epitope with the heptamer sequence HLTFGPG was detected and named RASFp1. Very similar and partly identical sequences are found in the variable region of lg kappa light chains in position 96-101, at the junction of framework 2 and the J-region. The antibody FKN-E12 was shown to detect the epitope RASFp1 also on human lgG kappa chains, but only in a specific conformation. The aim of the present study was to analyse human sera from patients with autoimmune diseases, non-autoimmune inflammatory diseases and healthy blood donors for the presence of lgG binding to RASFp1. For this purpose a 15-mer-peptide was synthesized containing RASFp1 within Vk-derived flanking regions, and an ELISA assay established. Sera of 142 individuals were studied. Only5% of the control sera including sera from patients with non-autoimmune inflammations were positive. In contrast, 45% of sera from patients with RA or SLE contained RASFp1-binding antibodies. Within the 40 RA sera analysed so far, rheumatoid factors and RASFp1-binding antibodies have shown no correlation with each other.

□ Fragestellung Im rheumatischen Gelenk finden sich transformiert erscheinende Fibroblasten an der Invasionszone in den Knorpel und Knochen. Uber die Faktoren, die zu diesem aggressiven Phanotyp fuhren, ist bisher wenig bekannt. Ziel der Untersuchungen war daher, mittels RAP-PCR (RNA arbitrarily primed PCR) zwischen rheumatoiden Fibroblasten und Osteoarthritis-Fibroblasten differentiell exprimierte Gene zu erfassen.

Background: Surveillance of patients with Barrett's esophagus or ulcerative colitis for dysplasia is confined to biopsy specimens taken randomly during endoscopy because dysplasia remains undetectable by visual inspection. We attempted to visualize dysplastic tissue during endoscopy after sensitization with 5-aminolevulinic acid (5-ALA) leading to accumulation and formation of protoporphyrin IX and induction of characteristic red fluorescence of the latter substance using blue light illumination. Methods: Six patients with histologically proven low- or high-grade dysplasia (Barrett's esophagus 2, ulcerative colitis 1, Billroth-II stomach 1, rectal polyps 2) were treated with oral administration of different concentrations of 5-ALA (10 to 20 mg/kg) or by local instillation of 3 gm 5-ALA in the rectum. Endoscopic fluorescence detection was performed 1 to 6 hours after sensitization using a blue light source and compared with conventional white light endoscopy. Biopsies of fluorescent and nonfluorescent areas were compared with histologic findings. Results: Normal duodenal mucosa and squamous epithelium showed more intense 5-ALA–induced background red fluorescence compared with normal mucosa in the stomach or Barrett's mucosa. Histologically, dysplasia was exclusively found in areas with red fluorescence. False-positive fluorescence was associated with microscopic inflammation of the mucosa or feces in the colon. Conclusions: 5-ALA–induced protoporphyrin IX fluorescence may be useful in the detection of dysplasia in the gastrointestinal tract by enhancement of endoscopic surveillance of patients at a high risk for dysplasia.

Several techniques are available to purify circulating blood monocytes for research. CD14-containing MicroBeads are suitable and reliable tools to reproducibly isolate human monocytes with a high purity but are quite expensive. This report describes that a comparable number of highly pure monocytes can be isolated from samples using up to tenfold lower amounts of CD14-MicroBeads. MicroBeads are widely used to isolate different cell populations and with this report more researchers may be encouraged to use this highly efficient, low-cost and thus affordable method to pursue their scientific goals.

Chronisch entzundliche Darmerkrankungen werden haufig von extraintestinalen Manifestationen begleitet, die zusammen mit Diarrhoen und Schmerzen zu einer deutlichen Beeintrachtigung der Lebensqualitat fuhren konnen. Ziel dieser Studie war es, Daten zu Erstsymptomen, extraintestinalen Manifestationen und Schwangerschaftsverlaufen aus einem grosen Patientenkollektiv des suddeutschen Raumes zu gewinnen. Daten von 392 Patienten aus den Jahren 1975 bis 1989 wurden analysiert und teilweise mit aktuelleren Daten eines anderen Kollektivs von 211 Patienten (1992 bis 1995) verglichen. Patienten mit Morbus Crohn waren zum Zeitpunkt der ersten Symptome im Schnitt 25 Jahre, diejenigen mit Colitis ulcerosa 30 Jahre alt. Die Gruppe der Patienten mit besonders langer Latenz zwischen ersten Symptomen und der, Erstdiagnose (>1 Jahr) hat sich bei Morbus Crohn deutlich verkleinert, umfast aber immer noch 38%, wohingegen nur 23% der Kolitispatienten langer als ein Jahr ohne Diagnose waren. Fuhrende erste Symptome beim Morbus Crohn waren Unwohlsein, Schmerzen und unblutige Diarrhoen, wahrend die Colitis ulcerosa sich meistens mit blutigen Durchfallen manifestierte. 64,6% der Patienten mit Colitis ulcerosa und 76,0% der Crohn-Patienten entwickelten extraintestinale Manifestationen. 15 von 37 Schwangerschaften bei Morbus Crohn und sechs von zehn der Schwangerschaften bei Colitis ulcerosa waren durch Komplikationen gepragt. Eine bessere Kenntnis der Initialsymptome und der extraintestinalen Manifestationen konnte den Anteil extrem langer Latenzen vom Auftreten der Symptomatik bis zur Diagnose verringern. Schwangere Patientinnen mit chronisch entzundlicher Darmerkrankung bedurfen einer intensivierten Uberwachung.

PURPOSE To evaluate the success of percutaneous, CT-guided abscess drainage (PAD) in patients with Crohn's disease. METHODS Within the last 5 years 8 patients with Crohn's disease were treated by PAD for intra-abdominal abscesses. A fistula was determined to be the cause in 4 patients. The abscesses arose spontaneously in 7 patients while one patient had a postoperative abscess. We used single lumen 10 F- and double lumen 12 F- and 14 F-catheters for drainage (duration of drainage 8-20 days). RESULTS In all cases the abscess was successfully drained by PAD. However, an operation-free interval of at least three months was achieved in only two patients. A healing of the fistula was not attained in any of the 4 patients with a proven fistula. No enterocutaneous fistulas arose within the course of PAD. CONCLUSIONS PAD is also useful for patients with Crohn's disease since it improves the starting situation for the necessary operative interventions. In most cases (especially with enterogenic fistulas), however, a long-lasting therapeutic result cannot be expected.

Background Microsatellite instability (MSI) is a new mechanism described in carcinogenesis of several tumours and seems to predispose for cancer in some chronic inflammatory diseases. As thyroiditis is thought to be both the cause and the consequence of thyroid carcinoma, it was the aim of this retrospective study to investigate the epidemiology and the influence of a coexistent thyroiditis on prognosis and clinicopathological parameters in an iodine-deficient area. Methods The grade of lymphocytic infiltration (LI) of 153 thyroid carcinomas was determined in paraffin-embedded tissues: G0 = no LI, G1 = peritumoral LI, G2 = peritumoral LI with follicle, G3 = diffuse LI. A non-radioactive PCR-based screening method was used for detection of MSI. Results Twenty-seven (17.7%) out of 153 carcinomas were accompanied by thyroiditis (G1, 16; G2, 5; G3, 6). Ten cases fulfilled the criteria necessary for diagnosing Hashimoto's thyroiditis. Nine out of 10 (90%) Hashimoto's cases and 16 out of 17 (94%) other thyroiditis cases were associated with a significantly (χ2

Polyarteritis nodosa (PAN) is a vasculitis of unknown aetiology, characterized by segmental, necrotizing, transmural inflammation of medium‐sized vessels. A prevalence of 30.7 per million has been ...

A 46-year-old woman developed rapidly worsening renal insufficiency. Extensive calcification of the kidneys was found. The patient also suffered from ischaemic neuropathy, myopathy and arthritis. In a muscle biopsy multiple calcium oxalate crystals could be demonstrated surrounded by inflammatory infiltrates. Levels of oxalate in serum were markedly elevated. Diagnosis of primary hyperoxaluria type I was made by measuring alanine/glyoxylate aminotransferase activity in a liver biopsy. The patient underwent kidney transplantation twice, but each of the transplants failed after a very short time owing to hyperacute rejection and rupture of the organ, respectively. Eventually, combined liver/kidney transplantation was successfully performed. Two years after the transplantation, both organs work with good function. This case of primary hyperoxaluria type I is remarkable for the late onset of symptoms and the extensive involvement of other organ systems in addition to the kidneys. This case presentation confirms previous reports discouraging isolated kidney transplantation for patients with primary hyperoxaluria. Only combined liver/kidney transplantation can correct the metabolic defect and may give these patients superior long-term benefit.

Drug treatment does not play a significant role either in the maintenance of remission induced by drugs or surgery in Crohn's disease. Considering the data available, it is reasonable that after resection of involved bowel segments an attempt is made to avoid relapses using a suitable 5-ASA preparation. This remains an individual decision following explanation of the pros and cons of the treatment to the patient. The application of immunosuppressants such as azathioprine or 6-mercaptopurine is probably more effective but hampered by a higher rate of side effects. This approach is therefore not to be generally recommended at this time. New approaches such as antibodies against tumor necrosis factor are of interest but can also currently not be recommended for practical treatment. In conclusion, at this time no drug can be recommended for remission maintenance which is safe and effective. The use of the different possibilities described remains at the discretion of the treating physician depending on the individual situation (localization of disease, extent of operative intervention and history regarding relapses). Only a better understanding of etiology and pathogenesis and possible subtyping of patients with Crohn's disease can lead to better and more effective measures of remission maintenance.

Es durfte wohl an den weitgehend fehlenden klinischen Symptomen liegen, das man dem Pankreas im Rahmen des Schockgeschehens bisher keine grosere Beachtung zugewandt hat. Das scheint angesichts der Haufigkeit pankreatischer Veranderungen im Schock allerdings nicht gerechtfertigt. Die vorliegende Ubersicht erlautert sehr plausibel die wahrscheinlichen und gesicherten pathogenetischen Schritte, die uber eine gestorte Makro- und Mikrozirkulation zur schweren Pankreasschadigung im Sinne einer odematosen oder – im schlimmsten Fall – nekrotisiertenden Pankreatitis fuhren durften. Konsequent ergeben sich daraus therapeutische Optionen, die hier ebenfalls dargestellt werden. Sicherlich wird man bei kunftigen Therapiestrategien der Schockbekampfung auch die moglichen Pankreasveranderungen mehr als bisher in Betracht ziehen mussen.

SUMMARY Macrophages play an important role in the intestinal mucosal immune system. However, they are a poorly defined cell population. We therefore determined their phenotype in normal colonic mucosa. Macrophages were isolated from colonic biopsies and surgical specimens by collagenase digestion. Colonic macrophages were positively sorted by anti-CD33 magnetic beads. Flow cytometric triple fluorescence analysis was applied to study CD14, CD16, CD33, CD44, CD11b, CD11c, CD64, HLA-DR, CD80, CD86 and CD3/CD19 expression. CD33 was evaluated as a positive marker for intestinal macrophages. CD33+ cells isolated from normal colonic mucosa showed co-expression of the established intracellular macrophage marker CD68 in FACS analysis. CD33+ cells were capable of phagocytosis. Isolation of this cell population by magnetic anti-CD33 beads and culture resulted in a 4·2–40-fold increase in IL-1β and 4·5–44-fold increase in tumour necrosis factor-alpha (TNF-α) secretion compared with unsorted lamina propria mononuclear cells (LPMC). Of the CD33+ cells, 90·9 ± 6·9% (mean ± s.d.) were CD44+. However, macrophages from colonic mucosa showed only a low expression of CD14 (10·5 ± 3·8%), CD16 (10·1 ± 3·9%), HLA-DR (27·3 ± 9·2%), CD11b (17·4 ± 6·8%), CD11c (17·8 ± 10·4%). Furthermore, expression of CD80 (9·2 ± 4·2%) and CD86 (15·1 ± 7·3%) was low, suggesting a low ability of normal intestinal macrophages to activate T cells and T cell-mediated immune responses. We conclude that CD33 is useful for the isolation and flow cytometric characterization of colonic macrophages. These cells exhibit a single phenotype in normal mucosa (CD33++, CD44++, CD14−, CD16−, CD11b−, CD11c−, HLA-DRlow, CD80−, CD86−) lacking lipopolysaccharide (LPS) receptor and costimulatory molecules.

Die bakterielle Fehlbesiedelung des oberen Dunndarms, die bei Leberzirrhose haufig anzutreffen ist und zu der Aszites geradezu pradisponiert, durfte zum Entstehen der spontanen bakteriellen Peritonitis (SBP) wesentlich beitragen. Mangelernahrung, Storungen der unspezifischen und spezifischen regionalen Abwehr spielen dabei ebenfalls eine wichtige Rolle. Bemerkenswert erscheint die nachgewiesene Erhohung von Interleukin-6 und anderen Makrophagen-assoziierten Zytokinen in der der Aszitesflussigkeit. Das Krankheitsbild der SBP wird in dieser Ubersicht eingehend unter den Gesichtspunkten der Epidemiologie, Klinik, Risikofaktoren, Pathogenese, Diagnostik, Prognose, Therapie sowie Rezidiv- und Primarprophylaxe abgehandelt. Neben einer umfassenden Literaturubersicht stutzen sich die Verfasser auch auf Untersuchungen ihres eigenen umfangreichen Krankengut. Am Beispiel der SBP sei wieder einmal daran erinnert, das eine Komplikation, hier als eine Peritonitis bei Aszites, zwar lange bekannt sein kann, als Krankheitsentitat aber viel spater erkannt und ausfuhrlich beschrieben wird. Das trifft auf die SBP zu. So steht zu erwarten, das das Krankheitsbild der spontanen bakteriellen Peritonitis fur manche unserer nicht spezialisierten Leser ganz einfach noch nicht in das arztliche Gesichtsfeld getreten, also schlicht gesagt: neu ist.

Chronisch entzundliche Darmerkrankungen gehen haufig mit einem zunehmenden Mangel an Spurenelementen und Vitaminen einher. Ziel unserer Studie war es, retrospektiv an einem grosen Patientengut die Haufigkeit dieses Problems sowie von hepatischen und renalen Komplikationen zu evaluieren. Die Krankenakten von 392 Patienten der Jahre 1975 bis 1989, davon 279 mit Morbus Crohn (160 Frauen, 119 Manner) und 113 mit Colitis ulcerosa (56 Frauen, 57 Manner) wurden retrospektiv ausgewertet. 85% der Crohn-Patienten wiesen im Laufe der Erkrankung Mangelzustande auf gegenuber 68% derjenigen mit Colitis ulcerosa. Am haufigsten war bei beiden Erkrankungen der Eisenmangel, gefolgt von erniedrigten Serumkonzentrationen von Calcium, Zink, Eiweis, Vitamin B12, Magnesium und Folsaure. 38% der Morbus-Crohn-Patienten und 27% derjenigen mit Colitis ulcerosa hatten mindestens einmal pathologisch erhohte Leberfunktionsparameter. Am haufigsten waren erhohte Serumaktivitaten von γGT und GPT, gefolgt von AP und GOT und erhohten Bilirubinkonzentrationen. Gallensteine hatten 12% der Patienten mit Morbus Crohn und 4% der mit Colitis ulcerosa. Nierensteine waren bei 6% der Morbus-Crohn-Patienten und bei 4% der Patienten mit Colitis ulcerosa nachweisbar. Die Haufigkeit extraintestinaler Komplikationen, insbesondere von Mangelzustanden, macht die Notwendigkeit einer regelmasigen Kontrolle dieser Patienten auch unter diesem Aspekt deutlich. Die Tatsache, das die abnormen Leberfunktionsparameter meist passager waren, last eine Abklarung derselben nur bei protrahiertem Verlauf notig erscheinen.

Detecting the source of obscure gastrointestinal bleeding can be difficult. Capsule endoscopy is a promising diagnostic tool for investigating patients with this condition, although identifying the source of intermittent or low-grade bleeding remains a diagnostic challenge. We present case reports of two patients with obscure gastrointestinal bleeding, in whom the source of recurrent bleeding episodes was diagnosed by capsule endoscopy while they were on anticoagulation therapy. The first patient, an 81-year-old white woman, was on long-term oral anticoagulation because she had chronic atrial fibrillation. Capsule endoscopy demonstrated a bleeding tumor in the region of the terminal ileum. The second patient, a 59-year-old white man, underwent an initial capsule endoscopy, which was negative. After initiation of anticoagulation with heparin, a second capsule endoscopy procedure in this patient revealed several small bleeding lesions in the proximal small bowel. In both cases a gastrointestinal stromal tumor was identified as the bleeding source and was resected. These two cases demonstrate that provocation of bleeding during capsule endoscopy may increase its sensitivity.

□ BackgroundDuring the last years, examination of autonomic nervous function and of autonomic neuropathy has attracted attention not only in diabetes mellitus research but also in other areas of internal medicine. However, patients with various chronic diseases with autoimmune phenomenons have never been investigated in a comparative study with standardized examination techniques. Hence, the aim of the study was to examine the prevalence and the severity of autonomic neuropathy in patients with the following chronic diseases.□ Patients and MethodsWe investigated 28 patients with Crohn’s disease (CD; age: 32.4±2.0 y), 17 patients with ulcerative colitis (UC; 39.7±3.6 y), 39 patients with systemic lupus erythematosus (SLE; 34.9±2.0 y), 38 patients with progressive systemic sclerosis (pSS; 51.5±2.4 y) and 65 patients with insulin-dependent diabetes mellitus (IDDM; 35.5±1.6 y). Cardiovascular autonomic (cANP), pupillary autonomic (pANP), and sensorimotor (ssNP) neuropathy were assessed by standardized techniques.□ ResultsPrevalence rates for cANP, pANP and ssNP were found to be 0%, 19%, and 7% in CD, 6%, 25%, and 18% in UC, 5%, 29%, and 10% in SLE, 11%, 16%, and 32% in pSS, and 26%, 66%, and 29% in IDDM, respectively.□ ConclusionThe study demonstrated patients with IDDM to have the highest prevalence rates of cANP and pANP. Patients with other chronic diseases, particularly SLE, pSS and UC, had high prevalence rates of pANP. This may be due to alterations of structures of the central nervous system in these patients. cANP was rare in patients with inflammatory bowel disease and ssNP was found very often in patients with pSS, probably due to local fibrotic lesions. The various disease groups differ in the pattern and severity of autonomic and sensorimotor neuropathy, which indicates that different structures and neuropathogenic mechanisms may be involved.

PURPOSE: This study was designed to compare esophageal and anorectal function parameters in patients with systemic sclerosis and to define the role of anorectal manometry in the diagnosis of gastrointestinal involvement of systemic sclerosis. PATIENTS AND METHODS: Twenty-six consecutive patients (22 females) with systemic sclerosis originally referred for assessment of esophageal function were evaluated by esophageal and anorectal manometry. Anorectal function parameters were compared between patients with normal and those with disturbed esophageal function. RESULTS: A total of 17 of 26 patients (65 percent) had severe esophageal dysfunction with aperistalsis of the lower two-thirds of the esophagus, whereas 9 patients (35 percent) had normal esophageal manometry. Only three patients (11.5 percent) suffered from occasional fecal incontinence. Anorectal function parameters (resting pressure, maximum squeeze pressure, perception threshold) were not significantly different between patients with normal and those with disturbed esophageal motility. Rectoanal inhibitory reflex was excitable in nearly 90 percent of patients. CONCLUSION: In an unselected group of patients with systemic sclerosis, fecal incontinence and abnormal anorectal function are rather rare findings. Anorectal manometry cannot differentiate between patients with and without gastrointestinal involvement of systemic sclerosis.

In der vorliegenden Arbeit wird ein Uberblick uber die Stufendiagnostik bei sonographisch nachgewiesenen Herdbefunden in der Leber gegeben. Richtungweisend fur das auch in Algorithmen dargestellte Vorgehen ist, ob ein extrahepatischer Tumor bekannt ist oder nicht. So sollten typische Zufallsbefunde („Inzidentalome”) keine weitere Diagnostik auslosen. Zu weiterfuhrenden Diagnostik sei neben der Computer- und Magnetresonanztomographie besonders auf die CT-Arterioportographie hingewiesen. Auch szintigraphische Methoden haben einen hohen Stellenwert, z.B. die Blutpoolszintigraphie mit 99mTc markierten Erythrozyten oder die Funktionsszintigraphie mit 99mTc markierten Substanzen. Die Kernspintomographie mit supraparamagnetischem Eisenoxid, das in den Kupffer’schen Sternzellen des normalen Lebergewebes gespeichert wird, ermoglicht durch den Kontrastunterschied die Unterscheidung zu malignen Strukturen wie hepatozellularen Karzinomen oder Metastasen, in denen sich keine Kupffer’sche Sternzellen finden.

Intestinal macrophages play an important role in mucosal inflammation. In normal colonic mucosa we recently demonstrated a unique macrophage phenotype with attenuated immune functions. Here we present an analysis of the alterations of the phenotype of colonic macrophages in inflammatory bowel disease (IBD).Intestinal macrophages were isolated from biopsies of patients with IBD (n =20). Flow cytometric triple fluorescence analysis was applied to study CD14, CD16, CD33, HLA-DR, CD44, CD11b, CD11c and CD3/CD19 expression.In IBD there was an increase in expression not only of CD14 compared to control mucosa (36.0% +/- 13.2% vs. 10.5% +/- 3.8%, P0.0001) but also of CD16 (28.6% +/- 10.3% vs. 10.1% +/- 3.9%, P0.0001), HLA-DR (53.1% +/- 15.9% vs. 27.3% +/- 9.2%, P0.0005), CD11b (42.8% +/- 14.2% vs. 17.4% +/- 6.8%, P0.0001) and CD11c (35.1% +/- 15.9% vs. 17.8% +/- 10.4%, P0.005.). Furthermore, a hitherto undescribed new population of macrophages could be detected by flow cytometry only in patients with ulcerative colitis (CD16++, CD11b++, CD14(low), CD33(low), CD11c-) accounting for 5.8% of all cells isolated.In contrast to colonic macrophages from normal mucosa, there is a significantly higher expression of CD14, CD16, HLA-DR, CD11b and CD11c in IBD, indicating additional macrophage populations in the inflamed mucosa. This may reflect either a recruitment of new cells from the circulation or a change in phenotype of resident cells.

Effective medical treatment of ulcerative colitis is available. However, 20-40% of patients remain refractory and become steroid dependent, or have chronic activity. Azathioprine and its metabolite 6-mercaptopurine have been found to be effective in this setting, although duration of treatment and doses are not entirely clear. Neither is widely used in Europe for this indication. Methotrexate has no definitive place in the treatment of refractory colitis. Intravenous cyclosporin A induces remission in a considerable number of patients; follow-up treatment is, however, not defined. This approach may be useful to allow elective surgery. A number of other treatments have been proposed including chloroquine, interferons and anti-cytokines. None of these can currently be recommended for clinical practice. Anti-inflammatory cytokines such as interleukin-10 may be good candidates.

□ Hintergrund Zwischen 1972 und 1984 hat sich das diagnostische Arsenal bei Verdacht auf Erkrankungen des Abdomens durch breite Anwendung der Endoskopie, dann der Sonographie und schlieslich der Computertomographie wesentlich geandert.

Der immunsuppressiven Therapie kommt bei chronischen Darmerkrankungen grose Bedeutung zu, insbesondere dort, wo die Standardtherapie nicht den gewunschten Erfolg zeigt. Als Therapie der ersten Wahl gelten bei Colitis ulcerosa 5-Aminosalizylsaure-freisetzende Medikamente, bei Morbus Crohn Kortikosteroide. Innerhalb der Gruppe immunsuppressiver Praparate gibt es erhebliche Wirkungsunterschiede. Daruber hinaus ist die Immunsuppression auch mit ernstzunehmenden Nebenwirkungen belastet. Uber den Stellenwert der Immunsuppression als Erganzung, mogliche oder bei Unvertraglichkeit notwendige Substitution der Standardtherapien von Colitis ulcerosa und Morbus Crohn wird hier eingehend referiert. Auch die Behandlung dieser Erkrankungen in der Schwangerschaft wird dabei erlautert.

Glukokortikoide sind wirksame Medikamente zur Behandlung der Colitis ulcerosa. Das Auftreten von Nebenwirkungen ist von der Dosis und Dauer der Behandlung abhangig und kann bei langjahriger Einnahme bis zu 80% betragen. Eine seltene unerwunschte Wirkung der Glukokortikoidtherapie ist die steroidinduzierte Myopathie. Es existiert eine akute und eine chronische Form. Die chronische Steroidmyopathie betrifft vornehmlich die Muskulatur des Schulter- und Beckengurtels und ausert sich in einer proximalen Muskelschwache. Histologisch findet sich eine Atrophie der Typ-IIb-Muskelfasern. Die chronische Steroidmyopathie entsteht nach langerer Einnahme einer mittleren bis hoheren Dosis von Glukokortikoiden. Eigener Fall: In der vorgestellten Kasuistik, entwickelte ein 25jahriger Patient mit linksseitiger Colitis ulcerosa nach monatelanger Glukokortikoidbehandlung eine chronische Steroidmyopathie. Nach Umstellung von der oralen systemischen Steroidbehandlung auf Budesonid besserte sich die Myopathie. Die linksseitige Colitis ulcerosa blieb in Remission. Schlusfolgerung: Der Fall dokumentiert das Verschwinden einer bedeutsamen Steroidnebenwirkung nach Umstellung von einer systemischen Steroidtherapie auf Budesonid.

The role of bile acids in the pathogenesis of bowel inflammation is unknown. The objective of this study was to determine whether urso- (UDC), cheno- (CDC), and taurochenodeoxycholic acid (TCDC) exert a pro- or antiinflammatory action in the acute and chronic phase of the indomethacin model of a long lasting ileitis in rats. Short-term and long-term inflammatory responses (48 h and 10 days, respectively) after two subcutaneous indomethacin (Indo) injections were elicited in rat small bowel and mesentery. To distinguish between common and model-specific effects bile acids were tested also in another model of acute inflammation induced by mesenteric supervision with leukotriene B4(LTB4). The number of adherent and emigrated leukocytes, leukocyte rolling velocity, and venular wall shear rate were monitored in normal and inflamed postcapillary venules, and fecal pH of ileal contents which has been shown to correlate with degree of inflammation was measured. 6.5- and 2.3-fold increases in leukocyte adherence and comparable increments in leukocyte emigration were observed 48 h and ten days after indomethacin treatment, respectively. UDC, CDC, and TCDC (10 mg/kg) given daily from Indo administration until the experiment attenuated the leukocyte adherence and emigration responses elicited by indomethacin in short- and long-term inflammation. This effect was accompanied by a significant increase of fecal pH which had been lowered by indomethacin. None of the bile acids reduced the LTB4-induced increases in adherence and emigration. Oral administration of UDC, CDC, and TCDC reduces leukocyte adhesion and emigration in acute and chronic stages of Indo-induced inflammation. This could be due to the alkalizing effect of these bile acids on fecal pH which has been shown to correlate with a decrease of leukocyte-endothelial cell interactions but—according to the missing effectiveness in another model of intestinal inflammation—not to specific influences on leukocyte-endothelial cell adhesion.

Ehlers-Danlos syndrome (EDS) type IV is an autosomal dominant connective tissue disease caused by mutations in the type III collagen gene resulting in extreme tissue fragility. Affected individuals are at risk of dramatic and often fatal complications, mostly spontaneous arterial, uterine, or colonic ruptures. Phenotypic expression of EDS type IV is variable and clinical signs are generally quite subtle, thus making a prompt diagnosis difficult. The case of a 33-year-old woman is described who presented with a wide range of clinical features and sequelae that eventually led to the diagnosis of EDS type IV. She presented with spontaneous liver rupture, renal infarction, and pneumothorax, all representing rare complications of EDS type IV. Prior history revealed a uterine rupture in advanced pregnancy associated with ischemic necrosis of the descending and sigmoid colon. EDS type IV should be suspected in young individuals who present with such unusual complications. Early diagnosis is essential if severe or even lethal complications are to be avoided in the diagnostic and therapeutic management of such patients.

More than one-third of patients with IBD are affected by extraintestinal manifestations or extraintestinal complications beyond the intestinal manifestation of the disease. The most common manifestations include arthropathies, mucocutaneous and ophthalmological manifestations, as well as conditions affecting the hepatobiliary system, both in Crohn's disease and ulcerative colitis. However, less frequent manifestations, such as pulmonary or neurological manifestations, should also be considered in patients with IBD. Several extraintestinal manifestations follow the course of the underlying intestinal activity, whereas others are independent from the intestinal inflammation. Extraintestinal complications such as iron-deficiency anaemia and osteoporosis are consequences of the intestinal disease or of disease-specific treatment. As extraintestinal manifestations and complications strongly influence quality of life, and to avoid severe complications, adequate treatment is mandatory in affected patients. We provide a comprehensive overview of different extraintestinal manifestations and complications, including their management, in patients with IBD.

In a previous study we demonstrated a superfusion technique which allows for investigation of nerve-immune cell interaction in murine spleen. We demonstrated that under septic-like conditions in the presence of bacteria and lipopolysaccharide (LPS), electrically induced inhibition of interleukin 6 (IL-6) secretion was attenuated by the beta-adrenergic antagonist propranolol. This effect was now investigated more closely under various endotoxin conditions in order to dissect effects of bacteria and endotoxin: (A) bacteria-rich conditions (without penicillin/streptomycin [P/S] and without LPS), (B) LPS-enriched conditions (with P/S and with LPS), and (C) bacteria-free conditions (with P/S and without LPS). Under bacteria-rich conditions, norepinephrine (Emax = 10(-6) M, p = 0.012) and isoproterenol (Emax = 10(-6) M, p = 0.048) concentration-dependently inhibited IL-6 secretion from murine spleen slices in contrast to bacteria-free conditions. In a bacteria-free environment the beta-adrenergic antagonist propranolol did not attenuate the electrically induced inhibition of splenic IL-6 secretion. The insertion of bacterial filters in front of the superfusion chambers to avoid direct contact between bacteria and cells increased the electrically-induced inhibition of IL-6 secretion (p = 0.0036). Added LPS did not change the electrically-induced release of norepinephrine from presynaptic nerve terminals in murine spleen. The study demonstrates two different beta-adrenergic effects on IL-6 secretion of murine spleen slices under bacteria-rich or bacteria-free conditions.

In diabetic patients, several factors contribute to volume expansion and have to be counteracted by humoral and neuronal feedback control systems. We investigated N-terminal proatrial natriuretic factor (ANF1-98) and digoxin-like immunoreactive factor (DLIF), which are two counteracting hormones, and their interrelationship, with additional consideration given to autonomic nervous function in diabetic patients. ANF1-98 and DLIF were measured in 64 diabetic patients. Autonomic nervous function was assessed using nine autonomic nervous function tests. The patients were subdivided into two groups, one with four or more (group 1) and one with less than four abnormal results in autonomic function tests (group 2). Compared with group 2, group 1 demonstrated detectable DLIF levels less often (17.2 vs. 45.7, P = 0.0195) and increased levels of ANF1-98 (mean +/- SEM: 850.0 +/- 108.8 vs. 554.8 +/- 45.9 pmol/L, P = 0.0099). However, the groups did not differ in blood pressure, daily sodium, and daily potassium excretion. The number of abnormal autonomic function tests correlated significantly with ANF1-98 (P = 0.0002). In patients with detectable DLIF, DLIF correlated with ANF1-98 (P = 0.0080). These results demonstrate close interactions between the autonomic nervous system and the two natriuretic hormones. In patients with autonomic nervous dysfunction, higher levels of ANF may possibly compensate for the lack of the natriuretic DLIF to counteract hypertension and chronic volume expansion.

OBJECTIVE To determine the age-independent impact of disease duration on autonomic nervous function in diabetic patients and to compare it with other disease-related complications. RESEARCH DESIGN AND METHODS Of the patients with diabetes, 166 (66 IDDM, 100 NIDDM) were investigated using standardized cardiovascular and pupillary test procedures, which provide 10 age-independent percentile values for each patient. Sensorimotor neuropathy was assessed using a standardized clinical examination, retinopathy by fundoscopy, and nephropathy using daily urinary protein excretion and creatinine clearance. RESULTS The duration of the disease did not correlate with the results of any one of six standard cardiovascular tests (P > 0.15). Pupillary parameters showed a weak negative correlation with disease duration (P < 0.04). Prevalence of cardiovascular autonomic dysfunction was not different in five different subgroups subdivided according to disease duration (0–6, 7–12, 13–18, 19–24, and ≥ 25 years), whereas prevalence of pupillary dysfunction changed significantly with disease duration (P = 0.016). In contrast, the prevalence of sensorimotor neuropathy (P = 0.006), retinopathy (P < 0.001), and proteinuria (P = 0.010) was significantly higher in patients with long-standing disease. Disease duration was not significantly different in patients without overall cardiovascular dysfunction, as compared with patients with dysfunction (15.6 ± 1.0 vs. 16.5 ± 1.5 years, P = 0.626). This was also found when considering overall pupillary dysfunction (14.5 ± 1.4 vs. 17.2 ± 1.0 years, P = 0.125). CONCLUSIONS Disease duration was not correlated with cardiovascular autonomic nervous function, whereas a correlation was observed with pupillary autonomic nervous function, sensorimotor neuropathy, retinopathy, and proteinuria. This may indicate that cardiovascular autonomic nervous function does not markedly change during the course of the disease. The question arises whether cardiovascular autonomic neuropathy may be more a functional abnormality than a structural lesion of the autonomic nervous system, which may be already present at the beginning, or even before, the manifestation of diabetes.

Objective : Previous studies have revealed large variations in the interobserver agreement of dysplasia grading in inflammatory bowel disease. Therefore, we investigated the diagnostic value of two novel monoclonal antibodies (MIB 1 against Ki-67 and PC 10 against PCNA) in the detection of dysplasia. Methods : A total of 62 biopsies were investigated and histologically classified as follows : 13 probably positive for dysplasia ; 15 low-grade dysplasia ; five high-grade dysplasia ; and 15 inflammation without dysplasia and 14 normal controls. The percentage of positive Ki-67- or PCNA-stained nuclei (= labelling index) was determined in relation to the distribution throughout the mucosa. Results : In all biopsies PCNA-labelling index exceeded that of Ki-67-labelling index. In the superficial half of the crypt PCNA- and Ki-67-labelling indices in the biopsies with 'indefinite for dysplasia, probably positive' or low-grade dysplasia exceeded that of normal tissue (P

The coinfusion of tauroursodeoxycholate (TUDC) prevents taurolithocholate (TLC) -induced cholestasis. 23-Methyl-ursodeoxycholate (MUDC) is a side-chain derivative of ursodeoxycholate (UDC). If conjugation with taurine is important for the protective effect of UDC, the MUDC may not be as able as TUDC to prevent TLC-induced cholestasis since it is poorly amidated by the liver. To answer this question, isolated livers of adult Sprague-Dawley rats were coinfused with MUDC (UDC, TUDC) and TLC. After 15 min, inflow rates of the bile acids were doubled. In further experiments taurine in excess was added to the coinfused bile acids. The uptake of bile acids was >90% in all groups, irrespective of whether they were perfused alone or in combination. Single perfusion of TLC caused a rapid decrease in bile flow. UDC and MUDC were hypercholeretic; TUDC moderately choleretic. During coinfusion experiments, TUDC not only completely abolished cholestasis but in addition increased bile flow and biliary bile acid secretion. UDC did prevent TLC cholestasis at the lower inflow rates. At high inflow rates, bile flow decreased significantly. Addition of taurine to this bile acid combination did not significantly improve the anticholestatic effect of UDC. At low and high infusion rates of MUDC, cholestasis induced by TLC was reduced very little. Cumulative bile flow over 30 min fell by approximately 70% as compared to that of singly perfused MUDC. Addition of taurine to the coinfused MUDC/TLC slightly, but less significantly, improved the anticholestatic effect of MUDC. Since MUDC is by far less protective than UDC (and TUDC) despite similar physiochemical properties, it is concluded that taurine conjugation of UDC seems to be a prerequisite to prevent TLC-induced cholestasis. The results imply that treatment of cholestatic liver diseases with taurine-conjugated UDC might be more appropriate than with unconjugated UDC in cases where taurine conjugation is defective or where taurine depletion has occurred.

Eine moderne Aszitestherapie sollte das Konzept einer Stufentherapie einhalten und in Anbetracht des palliativen Charakters als Therapieziel dem Patienten eine Verbesserung der Lebensqualitat bringen.

Immune defence mechanisms can be modulated by brain function. To study such interactions, an in vitro method was developed to examine the release of cytokines and norepinephrine (NE) after electrical stimulation. Slices of mouse spleen were placed in chambers with a volume of 80 μl and superfused with culture medium. To characterize electrically evoked NE release and cell viability a suitable stimulation protocol was developed using of [ 3 H]NE. As parameter for immune function, modulation of interleukin-6 (IL-6) release by the spleen cells brought about by electrical stimulation was investigated. Splenic [ 3 H]NE overflow was calcium-dependent, tetrodotoxin-sensitive and elicited by 54 mM potassium. Electrically evoked [ 3 H]NE release at 22 h was about 80% of the release at 5.3 h. Electrical stimulation substantially reduced IL-6 secretion at 6 h (control: 143.4 ± 14.3 vs. electrical: 71.3 ± 7.9 pg/ml/10 6 leukocytes, P = 0.0001). This effect was inhibited in a concentration-dependent manner by the β-adrenergic antagonist propranolol ( P = 0.0298, EC 50 approx. 10 −7 M). In conclusion, this new technique allows long-term investigation of cell function in slices of murine spleen. In addition, these are the first in vitro data indicating the presence of a functional neuroimmunological link in murine lymphoid tissue.