[Foreign research position in the career development of academic surgeons]. / Der Forschungsaufenthalt im Ausland im Berufsweg des akademischen Chirurgen.

Since there are no data concerning the results/efficiency of research stipends in foreign countries, the aim of this study was to analyze the experience of German surgeons doing research work abroad. Seventy-four fellows (residents) in surgical training who conducted research outside Germany between 1986 and 1995 were interviewed using a detailed questionnaire. Back in Germany, the results and experience gained from research abroad led in the majority of cases to a PhD degree ("habilitation"), a high number of publications, and intensified research efforts in the same field using the methods learned abroad. In Germany, better support for researchers in terms of better clinical and scientific perspectives is urgently needed according to numerous comments.

[Stoma prolapse and stoma retraction]. / Stomaprolaps und Stomaretraktion.

Prolapse and retraction of an intestinal stoma are postoperative complications which severely decrease the quality of life of patients and in some cases lead to an operative revision. Both entities should be treated with sophisticated care by specialized stoma therapists in the early phase in order to prevent secondary problems such as dermal ulceration. However, in case of additional problems, such as ileus, bleeding, incarceration or impossibility of adequate stoma care, an operative revision is indicated. It remains an individual decision whether a local or a transabdominal revision of the stoma is necessary.At present the level of information and the number of well designed studies dealing with prolapse or retraction of a stoma are unsatisfactory and there are merely studies which report on prolapse and retraction as an incidental finding rather than primarily focusing on these problems. In addition there is a lack of clear cut definitions for both entities which would allow a comparison of data obtained in different studies.There is clearly a demand for a structured scientific clarification as the occurrence of stomal retraction or prolapse may present psychological and medical problems for the patients and therefore needs to be treated, conservatively and/or operatively, by both stoma specialists and surgeons.

[Ostomy for stool deviation: indications and operative techniques]. / Deviationsstoma: Indikation und Techniken.

The deviation of feces is a very old and still largely applied technique used by general surgeons. Indications divide into elective and emergency operations. Among the elective cases, rectal carcinoma, extensive perianal fistulae and neurogenic disorders of the distal colon are the most common indications. In an emergency situation causes such as extensive peritonitis (e.g. due to anastomotic leakage) and extensive trauma to the pelvis/rectum quite often result in a stoma. All segments of the intestine, from the first loop after the ligament of Treitz down to the sigmoid colon, are feasible for a deviation procedure depending on the indications and the anatomical conditions. The decision whether to create a loop ostomy or a terminal stoma is reached with respect to the underlying indications and the anatomical and pathophysiological situation. The aim of the procedure is a complete and adequate stool deviation as well as a situation where the patient is able to take care of the ostomy in a convenient and reliable fashion while guided and educated by a stoma therapist. The prevention and treatment of complications, such as stoma necrosis or retraction are absolutely crucial in order to have satisfying long-term results and an acceptable quality of life.

[Are leukocytes and CRP early indicators for anastomotic leakage after esophageal resection?]. / Sind Leukozyten und C-reaktives Protein geeignete Parameter als Frühindikatoren der Anastomoseninsuffizienz nach Osophagusresektion?1.

BACKGROUND: Anastomotic leaks represent the most common severe postoperative complications after esophagectomy. In this study standard inflammatory laboratory parameters [leukocytes, C-reactive protein (CRP)] were evaluated as indicators for anastomotic leakage after esophagectomy. PATIENTS AND METHODS: Between 1 / 1997 and 12 / 2006 a total of 558 patients with esophageal cancer underwent an Ivor-Lewis esophagectomy. Among these patients, all those (n = 50, 8.9 %) suffering from an anastomotic leak were matched to 50 patients without anastomotic leakage. Leukocytes, CRP level and clinical parameters (body temperature, cardiac / respiratory problems, wound secretion) were retrospectively analysed at short-term intervals in both groups. RESULTS: Patients with anastomotic leaks showed significant continuously increased CRP levels and leukocyte counts from the second or, respectively, 5 (th) postoperative day onwards compared to patients without anastomotic leaks. Using a stepwise regression, an 80 % sensitivity for leakage detection has been calculated by a cut-off value for CRP set at 13.5 mg / dL from day 2 onwards or, respectively, for leukocytes at 10.5 Gpt / L from day 8 onwards. Concomitantly, patients with anastomotic leaks suffered significantly more from respiratory problems and abdominal pain. CONCLUSION: CRP appears to be a reliable and predictable indicator for anastomotic leakage after esophagectomy and should, therefore, be routinely used as a screening marker to provide a reason for extended diagnosis.

Mechanisms underlying the anti-inflammatory actions of boswellic acid derivatives in experimental colitis.

Recent clinical trials of the gum resin of Boswellia serrata have shown promising results in patients with ulcerative colitis. The objective of this study was to determine whether a semisynthetic form of acetyl-11-keto-beta-boswellic acid (sAKBA), the most potent anti-inflammatory component of the resin, also confers protection in experimental murine colitis induced by dextran sodium sulfate (DSS) to compare its effects with those standard medications of ulcerative colitis like steroids and to examine whether leukocyte-endothelial cell adhesion is a major target of action of sAKBA. Clinical measurements of disease activity and histology were used to assess disease progression, and intravital microscopy was employed to monitor the adhesion of leukocytes and platelets in postcapillary venules of the inflamed colon. sAKBA treatment significantly blunted disease activity as assessed both grossly and by histology. Similarly, the recruitment of adherent leukocytes and platelets into inflamed colonic venules was profoundly reduced in mice treated with sAKBA. Because previous studies in the DSS model have shown that P-selectin mediates these blood cell-endothelial cell interactions, the expression of P-selectin in the colonic microcirculation was monitored using the dual-radiolabeled antibody technique. The treatment of established colitis with sAKBA largely prevented the P-selectin upregulation normally associated with DSS colitis. All of the protective responses observed with sAKBA were comparable to that realized in mice treated with a corticosteroid. Our findings demonstrated an anti-inflammatory effect of sAKBA and indicated that P-selectin-mediated recruitment of inflammatory cells is a major site of action for this novel anti-inflammatory agent.

[Length of overseas research sojourn in the career path of academic surgeons]. / Der Forschungsaufenthalt im Ausland im Berufsweg des akademischen Chirurgen.

Since there are no data concerning the results/efficiency of research stipends in foreign countries, the aim of this study was to analyze the experience of German surgeons doing research work abroad. Seventy-four fellows (residents) in surgical training who conducted research outside Germany between 1986 and 1995 have been interviewed using a detailed questionnaire. Back in Germany, the results and the experience gained from research abroad led in the majority of cases to a post doctoral degree, a high number of publications, as well as to intensified research efforts in the same field, using the methods learned abroad. Back home, the possibilities of pursuing research were often compromised by clinical workload. In general, better support for researchers in terms of better clinical and scientific perspectives is urgently needed, a demand that is voiced in numerous comments.

[Importance of blade geometry for stability of fixation with short intramedullary nailing systems for the proximal end of the femur (gliding nail)]. / Die Bedeutung der Klingengeometrie für die Verankerungsstabilität bei kurzem Verriegelungsnagelsystem des proximalen Femurendes (Gleitnagel).

Three biomechanical examinations of the double-T blade of the gliding nail were performed. Under alternating load, also after 100,000 cycles and 2000 N load, no instability occurred after gliding nail osteosynthesis. The best relationship between the introduction forces of the blade (1.771-1.329 N) and the extraction forces (1.474-477 N) was seen after glass pearl treatment of the blade surface. Displacement of the plate in a sow bone femor head after 1000 cycles at 1500 N was 1.0-4.00 mm for a double-T blade, but 4.0-8.0 mm for a 10 mm screw like the gamma-nail screw.

[Can noninvasive gadolinium 3D MR subtraction angiography of visceral arteries replace conventional intra-arterial catheter angiography?]. / Kann die nichtinvasive Gadolinium 3D-MR-Subtraktionsangiographie der Viszeralarterien die konventionelle intraarterielle Katheterangiographie ersetzen?

Classic catheter angiography is compared with 3D gadolinium MR angiography for evaluation of the vascular anatomy of the celiac trunk, liver supplying arteries, and the portal venous system. Based on 10 patients, this study shows the value of this new non-invasive method of angiography for the diagnosis of visceral vascular anatomy. For this diagnosis MR angiography is expected to replace conventional angiography in the near future.

Effect of anti-CD11b (alphaM-MAC-1) and anti-CD54 (ICAM-1) monoclonal antibodies on indomethacin induced chronic ileitis in rats.

Leukocyte emigration from blood to sites of inflammation involves sequential interaction of specific adhesion molecules expressed by both leukocytes and endothelial cells. The central steps in leukocyte-endothelial adhesive interactions are leukocyte rolling, sticking, and transmigration. This study investigated the effect of monoclonal antibodies against CD54 (ICAM-1) and CD11b (alphaM-chain of MAC-1) on intestinal inflammation. Anti-CD54 and anti-CD11b were tested in rats with indomethacin-induced chronic ileitis. Macroscopic changes were assessed by a modified version of the Wallace et al. score. Leukocyte rolling and sticking were investigated by intravital microscopy. Results show that indomethacin administration led to a chronic inflammatory response characterized by significant increase (P<0.05) in rolling (from 5.41+/-2.87 to 32.41+/-15.03 100 microm(-1) s(-1)) and sticking (from 0.16+/-0.18 to 9.11+/-5.3 100 microm(-1) s(-1)) leukocytes. After antibody treatment only the anti-CD11b group showed significant (P<0.05) reduction in rolling (from 32.41+/-15.03 to 6.6+/-2.7 100 microm(-1) s-1) and sticking (from 9.11+/-5.3 to 0.07+/-0.09 100 microm(-1) s-1) leukocytes. This was also the case for macroscopic changes. Indomethacin led to a rise in the Wallace score from 0 to 4.29+/-0.76 points (P<0.05) and anti-CD11b to a reduction from 4.29+/-0.76 to 1.29+/-1.11 points (P<0.05). Anti-CD54 and combined anti-CD11b/CD54 administration was not followed by significant changes. Therefore we suggest that leukocyte-based CD11b but not endothelial-based CD54 contributes most to leukocyte adhesion in the setting of indomethacin-induced ileitis in rats.

[Measuring blood flow velocity in healthy and indomethacin-induced inflammation in rat small intestine serosa with FITC-marked erythrocytes]. / Flussgeschwindigkeitsmessung an gesunder und Indomethacinentzündeter Rattendünndarmserosa mittels FITC-markierter Erythrozyten.

Intravital microscopy was performed in normal and indomethacin-induced intestinal inflammation at serosal postcapillary venules of the small bowel in rats. Standard parameters of microcirculation as red blood cell velocity, diameter of venules, blood flow and adherent leucocytes were successfully investigated using FITC-labelled red blood cells. Since postcapillary venules are responsible for the venous drainage of the inflammed small bowel segments this method is reliable and effective for further investigation of intestinal microcirculation under special conditions such as intestinal inflammation.

ICAM-1 and VCAM-1 antisense oligonucleotides attenuate in vivo leucocyte adherence and inflammation in rat inflammatory bowel disease.

BACKGROUND: Recruitment of circulating cells to the inflamed intestine is modulated by adhesion molecules expressed on the surface of both leucocytes and endothelial cells. AIMS: The objective of this study was to test whether 2'-O-methoxyethyl chimeric antisense oligonucleotides directed against endothelial intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) can downregulate leucocyte-endothelial interactions and thereby attenuate inflammation in rat experimental ileitis. METHODS: Indomethacin (7.5 mg/kg ) was injected subcutaneously into Sprague-Dawley rats 48 and 24 hours prior to intravital microscopy. Animals were treated with either ICAM-1 (ISIS 17470), VCAM-1 (ISIS 18155), or scrambled control antisense oligonucleotides administered subcutaneously or intravenously in parallel with indomethacin. Leucocyte trafficking was observed in ileal submucosal collecting venules. Macroscopic and histological grades of inflammation were measured 48 hours after the first indomethacin application. ICAM-1 and VCAM-1 expression in ileal submucosal venules was detected by immunohistochemistry. RESULTS: Intravenous administration of ICAM-1 oligonucleotides 2 mg/kg (rolling leucocytes 5.7 (2.4)/0.01 mm(2) endothelial surface, adherent leucocytes 0.8 (1.1)) and VCAM-1 oligonucleotides 8 mg/kg (9.2 (4.4), 0.6 (0.8)) significantly reduced leucocyte adhesion compared with diseased controls (27.8 (5.3), 14 (4.4)) in a dose dependent manner whereas subcutaneous treatment did not. Correspondingly, macroscopic and histological inflammation was significantly decreased. ICAM-1 oligonucleotides markedly reduced endothelial ICAM-1 expression while VCAM-1 oligonucleotides clearly diminished endothelial VCAM-1 expression. CONCLUSIONS: Both ICAM-1 and VCAM-1 2'-O-methoxyethyl chimeric antisense oligonucleotides attenuate rat ileitis by downregulation of leucocyte adherence and thus are potential candidates for anti-inflammatory treatment in inflammatory bowel disease.

Acetyl-11-keto-beta-boswellic acid, a constituent of a herbal medicine from Boswellia serrata resin, attenuates experimental ileitis.

The gum resin extract from Boswellia serrata (H15), an herbal product, was recently shown to have positive therapeutic effects in inflammatory bowel disease (IBD). However, the mechanisms and constituents responsible for these effects are poorly understood. This study examined the effect of the Boswellia extract and its single constituent acetyl-11-keto-beta-boswellic acid (AKBA) on leukocyte-endothelial cell interactions in an experimental model of IBD. Ileitis was induced by two subcutaneous injections of indomethacin (7.5 mg/kg) in Sprague-Dawley rats 24 h apart. Rats also received oral treatment with the Boswellia extract (H15) or AKBA at two different doses (low and high) equivalent to recommendations in human disease over 2 days. Controls received only the carriers NaHCO3 (subcutaneously) and tylose (orally). Effects of treatment were assessed by intravital microscopy in ileal submucosal venules for changes in the number of rolling and adherent leukocytes and by macroscopic and histological scoring. Increased leukocyte-endothelial cell adhesive interactions and severe tissue injury accompanied indomethacin-induced ileitis. Treatment with the Boswellia extract or AKBA resulted in a dose-dependent decrease in rolling (up to 90%) and adherent (up to 98%) leukocytes. High-dose Boswellia extract as well as both low- and high-dose AKBA significantly attenuated tissue injury scores. Oral therapy with the Boswellia extract or AKBA significantly reduces macroscopic and microcirculatory inflammatory features normally associated with indomethacin administration, indicating that the anti-inflammatory actions of the Boswellia extract in IBD may be due in part to boswellic acids such as AKBA.