Acetyl-11-keto-β-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.     

Ist der Chirurg ein prognostisch relevanter Faktor nach der R0-Resektion kolorektaler Karzinome?

Background: R0-resection of the primary tumor with adequate margins of safety and regional lymphadenectomy remains to be the mainstem of curative therapy of colorectal cancer. Randomized, controlled multicenter trials have yielded exact data concerning adjuvant therapy following R0-resection. However, the prognostic value of the operative technique, the institution and the individual surgeon is under discussion. Material and Method: The recent surgical literature concerning this topic was evaluated together with the results of an own clinical trial. Main study criteria were the influence of surgical technique, treating institution and individual surgeon on the incidence of tumor recurrence and long-term survival after R0-resection of colorectal carcinoma. Result: Data from the literature support the hypothesis that compliance with the general rules of oncological surgery alone will not guarantee identical results in every institution. Details of surgical technique in different institutions as well as the technical abilities of individual surgeons are of prognostic relevance in colon cancer and even more in rectal carcinoma. Conclusion: Strict standardization and continuous monitoring of the operative technique and early interim's analysis of long-term results (utilizing surrogate endpoints) are mandatory to allow a similar quality of oncological surgery in different institutions and by different surgeons within one institution.     

The use of endoscopy in patients with gastrointestinal motility problems

Gastrointestinal motility disorders are a commonly encountered problem. Although some are associated with organic alterations, others are defined by their symptoms, and no anatomic or histologic organic changes are to be found. In most cases, the etiology is completely unclear. Endoscopy, with the option of obtaining biopsies for histopathologic evaluation, plays the most important role in the diagnostic workup, as it can exclude such lesions as tumors, ulcers, inflammatory processes, and diverticula and it helps to define the grade and extent of motility-associated diseases (e.g., GERD). Furthermore, endoscopic interventional procedures offer sufficient treatment of several motility-related disorders (e.g., achalasia, GERD, its associated diseases, secondary constipation).     

Excitatory amino acid receptor subtype agonists induce feeding in the nucleus accumbens shell in rats: opioid antagonist actions and interactions with μ-opioid agonists

Administration of μ-opioid receptor subtype agonists into the nucleus accumbens shell elicits feeding which is dependent upon the normal function of μ-, δ- and κ-opioid receptors, D₁ dopamine receptors and GABA_B receptors in the nucleus accumbens shell for its full expression. Whereas the AMPA antagonist, DNQX administered into the nucleus accumbens shell elicits a transient, though intense feeding response, feeding is elicited by excitatory amino acid agonists administered into the lateral hypothalamus. The present study examined whether excitatory amino acid agonists elicited feeding following administration into the nucleus accumbens shell of rats, whether such feeding responses were altered by opioid antagonist pretreatment, and whether such feeding responses interacted with feeding elicited by μ-opioid agonists. Both AMPA (0.25–0.5 μg) and NMDA (1 μg) in the nucleus accumbens shell significantly and dose-dependently increased food intake over 4 h. Both feeding responses were blocked by naltrexone pretreatment in the nucleus accumbens shell. The μ-opioid agonist, [D-Ala²,NMe-Phe⁴,Gly-ol⁵]-enkephalin in the nucleus accumbens shell significantly increased food intake which was significantly enhanced by AMPA cotreatment. This enhanced feeding response was in turn blocked by pretreatment with either general or μ-selective opioid antagonists. In contrast, cotreatment of NMDA and the μ-opioid agonist in the nucleus accumbens shell elicited feeding which was significantly less than that elicited by either treatment alone. These data indicate the presence of important interactions between excitatory amino acid receptors and μ-opioid receptors in the nucleus accumbens shell in mediating feeding responses in nondeprived, ad libitum-fed rats.     

Prognostic relevance of pathological sympathetic activation after acute thromboembolic stroke

OBJECTIVE: To evaluate the prognostic impact of early pathologic sympathetic activation after stroke. METHODS: The authors examined 112 consecutive patients (mean age, 69 years; 60 men) with their first brain infarction. A pathologic sympathetic activation was presumed if the initial norepinephrine level exceeds 300 pg/mL. In addition, involvement of the insular cortex, nighttime blood pressure changes, and several cardiovascular risk factors were determined. One-year outcome measures were mortality rate, cardiovascular and cerebrovascular events, and activities of daily living (Barthel index and Rankin score). RESULTS: Norepinephrine levels greater than 300 pg/mL, nighttime blood pressure increases, and insular involvement were associated with a lower Barthel index (p < 0.005) at the 1-year follow-up. By stepwise logistic regression analysis, insular infarction, serum norepinephrine concentration, right-sided infarction, and nighttime blood pressure increase were significant and independent predictors of an unfavorable functional outcome. Cox regression analysis showed a higher rate of cardiovascular and cerebrovascular events (hazard ratio, 2.9; 95% CI, 1.07; 6.83; p < 0.04) in patients with initially increased norepinephrine concentrations. CONCLUSIONS: The involvement of the insular cortex, the occurrence of a pathologic nighttime blood pressure increase, and an initially increased serum norepinephrine concentration are independent predictors of poor long-term outcome.     

Internal Fixation of Distal Femur Fractures with the Less Invasive Stabilizing System (LISS)

Objective Stable internal fixation of distal femur with an implant resisting angular forces. The technique is minimally invasive, relies on a monocortical screw fixation and obviates the need for bone grafting. Indications Distal femur fractures of types A and C according to the AO classification. Periprosthetic femur fractures after total knee and hip arthroplasty. Contraindications Local infection, osteitis. Surgical Technique For intraarticular fractures: anterolateral parapatellar approach to the knee joint, anatomic reduction and temporary fixation of the articular fragments with Kirschner wires. Closed reduction aligning the block of articular fragments with the shaft. Submuscular introduction of the LISS plate with the help of an aiming device and its adaptation of the femur. Through stab incisions the screws are inserted leading to a stable anochorage of the plate. For extraarticular fractures: stab incisions over the lateral femoral condyle. Results In a prospective study, results of 54 fresh fractures of the distal femur in 51 patients (28 men, 23 women) operated between February 1997 and February 2000 could be assessed. The patients' average age at the time of infury was 53 (20-93) years. 48 patients suffered from type 33 fractures. Six type 32 fractures were encountered. Ten fractures were open. Six patients fractured their femur above or below a total joint replacement. We noted the following complications: one heterotopic ossification, two deep thrombophlebites with lung embolism and three infections. A loosening of the proximal screws occurred in four patients. 40 patients could be followed up clinically and radiologically, of these 32 after more than 6 months and 27 after more than 1 year. The Neer score of the 27 patients examined after >1 year amounted to an average of 73.9 (33-88) points, with six excellent, 14 satisfactory, six unsatisfactory results and one poor result. The Lysholm score amounted to 80.5 (40-100) points.     

Systolic and Diastolic Properties and Myocardial Blood Flow in the Heterotopically Transplanted Rat Heart during Acute Cardiac Rejection

The aim of the study was to characterize the course of systolic and diastolic function, myocardial blood flow, and histologic changes during acute rejection in a model of heterotopic transplantation in rats. For this purpose isogenic Lewis-to-Lewis and allogenic DA (Dark Agouti)-to-Lewis rat cardiac transplants were studied 1 hour and 1, 3, and 5 days, respectively, after heterotopic intraabdominal transplantation. Myocardial tissue blood flow (MBF) was assessed by the hydrogen-clearance method. An implanted balloon was used to measure pressure–volume relations in the transplanted heart. Myocardial water content was determined at the end of the experiments, and histologic examinations were performed. The MBF recovered during the first day postoperatively in both groups and decreased again in the allogenic group after 3 and 5 days (p < 0.05); it remained stable in the isogenic group. Myocardial relaxation was already prolonged in the allogenic group after 3 days and deteriorated further. Left ventricular end-diastolic pressure progressively increased in the allogenic group, whereas it remained unchanged in the isogenic group up to 5 days. After recovery from ischemia, the left ventricular peak systolic pressure was stable in the isogenic group for the entire further observation period, but it significantly decreased in the allogenic group after 5 days (p < 0.05). Myocardial water content showed a significant increase in the allogenic group compared to that in the isogenic group after 5 days. In the allogenic group histologic examination confirmed mild to moderate rejection after 3 days and severe acute rejection after 5 days. Thus, after recovery from ischemia, mild to moderate cardiac rejection was associated with reduced MBF and impaired relaxation. In a typical sequence, generation of edema and impaired diastolic compliance were terminally followed by systolic dysfunction during severe rejection.     

Bedside Percutaneous Tracheostomy: Clinical Comparison of Griggs and Fantoni Techniques

Elective tracheostomy is widely considered the preferred airway management of patients on long-term ventilation. In addition to open tracheostomy, a number of percutaneous procedures have been introduced during the last two decades, among them techniques according to Griggs (guidewire dilating forceps, or GWDF) and to Fantoni (translaryngeal tracheostomy, or TLT). The aim of the study was to evaluate these two techniques in terms of perioperative complications, risks, and benefits in critically ill patients. A series of 100 critically ill adult patients on long-term ventilation underwent elective percutaneous tracheostomy, either according to the Griggs (n= 50) or Fantoni (n= 50) technique. Tracheostomy was performed under general anesthesia at the patient's bedside. The mean (±SD) operating times were short, 9.2 ± 3.9 minutes (TLT) and 4.8 ± 3.7 minutes (GWDF) on average. Perioperative complications were noted in 4% of patients during either TLT or GWDF and included massive bleeding, mediastinal emphysema, posterior tracheal wall injury, and pretracheal placement of the tracheostomy tube. With regard to oxygenation, pre- and postoperative arterial oxygen tension divided by the fraction of inspired oxygen (PaO₂/FiO₂) ratios did not vary significantly, and no perioperative hypoxia was noted regardless of the technique used. We conclude that both TLT and GWDF represent attractive, safe alternatives to conventional tracheostomy or other percutaneous procedures if carefully performed by experienced physicians and under bronchoscopic control.