Use of Probiotics as Prophylaxis for Postoperative Infections

Postoperative bacterial infections are common despite prophylactic administration of antibiotics. The wide-spread use of antibiotics in patients has contributed to the emergence of multiresistant bacteria. A restricted use of antibiotics must be followed in most clinical situations. In surgical patients there are several reasons for an altered microbial flora in the gut in combination with an altered barrier function leading to an enhanced inflammatory response to surgery. Several experimental and clinical studies have shown that probiotics (mainly lactobacilli) may reduce the number of potentially pathogenia bacteria (PPM) and restore a deranged barrier function. It is therefore of interest to test if these abilities of probiotics can be utilized in preoperative prophylaxis. These factors may be corrected by perioperative administration of probiotics in addition to antibiotics. Fourteen randomized clinical trials have been presented in which the effect of such regimens has been tested. It seems that in patients undergoing liver transplantation or elective surgery in the upper gastrointestinal tract prophylactic administration of different probiotic strains in combination with different fibers results in a three-fold reduction in postoperative infections. In parallel there seems to be a reduction in postoperative inflammation, although that has not been studied in a systematic way. The use of similar concepts in colorectal surgery has not been successful in reducing postoperative infections. Reasons for this difference are not obvious. It may be that higher doses of probiotics with longer duration are needed to influence microbiota in the lower gastrointestinal tract or that immune function in colorectal patients may not be as important as in transplantation or surgery in the upper gastrointestinal tract. The favorable results for the use of prophylactic probiotics in some settings warrant further controlled studies to elucidate potential mechanisms, impact on gut microbiota and influence on clinical management. The use of probiotics must be better delineated in relation to type of bacteria, dose and length of administration

Broad phenotypic spectrum in familial adenomatous polyposis; from early onset and severe phenotypes to late onset of attenuated polyposis with the first manifestation at age 72

<p>Abstract</p> <p>Background</p> <p>Familial adenomatous polyposis (FAP) is typically characterized by multiple colonic polyps and frequent extracolonic features. Whereas the number of colonic polyps has been linked to the <it>APC </it>gene mutation, possible genotype-phenotype correlations largely remain to be defined for the extracolonic manifestations.</p> <p>Methods</p> <p>Full genomic sequencing combined with multiplex ligation-dependent probe amplification was used to identify <it>APC </it>gene mutations, which were correlated to the clinical presentations.</p> <p>Results</p> <p>10 novel <it>APC </it>gene mutations were identified in 11 families. A broad spectrum of extracolonic manifestations was identified in most of these individuals. Two sisters with an insertion in codon 528 (c.1582_1583insGC) both showed severe phenotypes with classical polyposis, upper gastrointestinal polyps and thyroid cancer. A woman with a 3'<it>APC </it>mutation (c.5030_5031insAA) developed colon cancer at age 72 as the first manifestation of attenuated FAP.</p> <p>Conclusion</p> <p>With an increasing number of FAP families diagnosed, a broad and variable tumor spectrum and a high frequency of extracolonic manifestations are gradually recognized. We report novel <it>APC </it>mutations and present two FAP cases that suggest familial aggregation of thyroid cancer and demonstrate the need to consider attenuated FAP also among elderly patients with colon cancer.</p

On Lactobacillus plantarum 299v, bacterial translocation and intestinal permeability.

The gastrointestinal tract harbours a huge load of bacteria which exerts important biological functions to maintain health. In certain conditions the relation between commensal bacteria and pathogens may be set off balance, with an increase in number of pathogens and risk of bacterial translocation (BT). Disease and trauma may also render the intestinal barrier dysfunctional, inducing BT and increased permeability. Probiotic bacteria, i.e. living bacteria which, when ingested, exerts beneficial effects on the host, have been found to stabilize the intestinal mucosa and affect the intestinal microflora. The aim of this thesis was to study the effects of Lactobacillus plantarum 299v in relation to intestinal permeability and BT. In study I L. plantarum 299v normalized E. coli-induced permeability in distal ileum of rats. This effect was achieved with a more continuous supply of L. plantarum 299v, rather than intermittent or acute pretreatment. Study II showed that pretreatment with L. plantarum 299v prevented BT in rats rendered septic with LPS. The protective effect seemed to be dependent on the ability of L. plantarum 299v to adhere to intestinal mucosa, indicating competitive inhibition as a possible mechanism behind prevention of translocation. Moreover, treatment with prebiotics, without a probioticum, did not prevent translocation. In study III LPS-induced intestinal barrier dysfunction on rats was found to be regulated by P-selectin-dependent leukocyte recruitment. With anti-P-selectin antibody intestinal permeability was attenuated, as well as leukocyte rolling and adhesion. This indicates anti-P-selectin treatment as a mean of ameliorating barrier dysfunction in sepsis. Finally, in study IV, it was found that high doses of L. plantarum 299v given to patients undergoing colon surgery were not able to reduce translocation of selected enteric bacteria but seemed to have a stimulatory effect on bacterial load in the colon. Further, L. plantarum 299v could be given to patients with malignancy without risk of tumour proliferation. Taken together, the findings herein indicates a potential of L. plantarum 299v pretreatment in reducing BT and intestinal permeability and warrants further studies in the clinical setting

Critical role of P-selectin-dependent leukocyte recruitment in endotoxin-induced intestinal barrier dysfunction in mice.

Objective: To define the importance of leukocyte recruitment in endotoxin-induced gut permeability. Materials and methods: 31 male C57BL/6 mice were challenged with lipopolysaccharide (LPS). Ileal permeability was measured in Ussing chambers and leukocyte-endothelium interactions studied with intravital fluorescence microscopy after 18 h. Results: LPS caused a clear-cut increase in leukocyte accumulation and intestinal permeability. Immunoneutralisation of P-selectin not only reduced leukocyte recruitment significantly (54% reduction) but also abolished endotoxin-induced intestinal leakage. Intestinal levels of pro-inflammatory chemokines increased markedly in response to LPS but were not influenced by inhibition of P-selectin in vivo. Conclusion: The present study shows not only that endotoxin-induced leukocyte recruitment is mediated by P-selectin but also that sepsis-associated intestinal leakage in the gut is largely regulated by leukocyte accumulation. Thus, our novel data demonstrate a critical link between P-selectin-dependent leukocyte recruitment and gut barrier failure in endotoxemia

Diameter and compliance in the human common carotid artery--variations with age and sex

In this study, age and sex differences in diameter and compliance of the common carotid artery (CCA) were evaluated in 119 healthy subjects with a phase-locked echo-tracking system. The diameter and pulsatile diameter changes were measured, and pressure strain elastic modulus (Ep) and stiffness (beta) were calculated and used as the inverse estimate of compliance. The carotid diameter increased more rapidly in males and was larger than in females from 25 years of age. The relative diameter change was equal in both sexes, and decreased from 12% to 14% in younger subjects to approximately 5% in elderly subjects. Compliance decreased almost linearly and in parallel in males and females up to 45 years of age. Between 45 and 60 years the decrease was more marked in females than in males, whereas it was by far more marked in males between 60 and 70 years of age

Differences in mechanical properties of the common carotid artery and abdominal aorta in healthy males

PURPOSE: Vascular disease is differentiated throughout the vascular regions, with central arteries more prone to dilation and with peripheral arteries more prone to occlusive disease. In this study we investigated the diameter and compliance in the common carotid artery and abdominal aorta in healthy males at varying ages to assess potential differences in the aging process. METHODS: An ultrasound phase-locked echo-tracking system was used to determine differences in diameter and pulsatile diameter changes of the common carotid artery and abdominal aorta in 56 healthy Caucasian males ages 10 to 74 years. Pressure strain elastic modulus (Ep) and stiffness (beta) were calculated from diameter, pulsatile diameter change, and blood pressure obtained by the auscultatory method. Compliance was defined as the inverse of Ep and stiffness. RESULTS: The diameter of both common carotid artery and abdominal aorta increases not only when a person is a child, but also when they are between 25 and 70 years old. The dilation in adults seems to be more accentuated in the abdominal aorta (27%) than in the common carotid artery (17%). Ep and stiffness (beta) are higher in the common carotid artery when a person is 10 years of age (p < 0.01 and 0.05). However, during aging, Ep and stiffness (beta) increase to a higher extent in the aorta than in the common carotid artery, with a significantly higher Ep and stiffness (beta) in the aorta when a person is 45 years and older (45 years: p < 0.05 and p = NS; 60 years: p < 0.001 and p < 0.001; 70 years: p < 0.01 and p < 0.01). CONCLUSIONS: This investigation demonstrates regional differences in diameter change and compliance in the common carotid artery and abdominal aorta and implies that the abdominal aorta is more prone to degenerative changes than the common carotid artery. This may be one etiologic factor for the regional differences in vascular disease

Systemic interleukin-6 response to colorectal surgery originates from the bowel.

Background: Surgical trauma evokes a systemic cytokine response which is enhanced in patients with colorectal cancer. The aim of this study was to locate the origin of the systemic cytokine response to colorectal surgery. Methods: The concentrations of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) were analysed in systemic and mesenteric venous blood in 12 patients operated on with colorectal resections due to cancer or benign lesions. Immunohistochemical staining and analysis of tissue concentrations of IL-6 and TNF-alpha in homogenates from tumours and benign specimens were performed. Results: Mesenteric venous blood contained higher concentrations of IL-6 compared to systemic venous blood after resection, but not before. Tissue concentration of IL-6 was higher in the tumours compared to the benign specimens and immunohistochemistry revealed an abundance of IL-6 and TNF-alpha in malignant epithelium compared to benign mucosa. Conclusion: The higher concentration of IL-6 in venous blood from the mesenterium of the resected colonic segment compared to systemic levels, indicates that the bowel is the source of the IL-6 response to surgical trauma in colorectal surgery