Study of the efficacy of Coated VICRYL Plus Antibacterial suture (coated Polyglactin 910 suture with Triclosan) in two animal models of general surgery.

OBJECTIVES: To evaluate the efficacy in vitro and in vivo of a new antibacterial suture (PGAB) compared with a traditional braided suture (PG). Our primary goals were to study microbiological effectiveness and impact on wound healing of PGAB vs PG. Secondary goal was to analyze influence on inflammatory response. METHODS: In vitro study: clinical samples of Staphylococcus epidermidis, Staphylococcus aureus, S. hominis, Staphylococcus haemolyticus, Staphylococcus auricularis, Enterococcus faecalis, Corynebacterium spp. and Escherichia coli were studied. We also implanted a flat mesh in 10 minipigs, four incisions each (two PG and two PGAB) two contaminated with S. epidermidis and two not contaminated. Finally, we performed four colic anastomosis in each of 10 minipigs, two contaminated with E. coli and two not contaminated (two PG and two PGAB). We studied the inflammatory and wound healing processes in both models. RESULTS: We observed a bactericidal efficacy of PGAB against grampositive, and bacteriostatic effect against E. coli. Mesh study: recovered CFU were lower in the group PGAB vs PG. In the group PGAB, inflammatory mediators' concentrations were lower. In the group PGAB, concentrations of wound healing mediators were normal. Colic anastomosis: recovered CFU were lower in the group PGAB vs the group PG. In the group PGAB we observed a reduction of inflammatory mediators. In the group PGAB we observed normalized concentrations of wound healing mediators. CONCLUSIONS: This study demonstrates microbiological efficacy of PGAB, that normalizes wound healing process, and an anti-inflammatory effect.

[Enteral nutrition with peri-surgery immunomodulating diet]. / Nutrición enteral con dieta inmunomoduladora perioperatoria.

OBJECTIVE: To assess the nutritional peri-surgical status of patients suffering from esophageal or gastric cancer, treated with esophagectomy and total gastrectomy, respectively, and to analyze the impact of an enteral immunomodulating diet on postsurgical complications. SETTING: Patients admitted to the Surgery Department of Hospital Clinico Universitario of Salamanca. PATIENTS AND METHODS: Patients submitted to esophagectomy and/or total gastrectomy to whom early enteral nutrition (EN) is provided with an immunomodulating diet. INTERVENTIONS: All patients were prescribed an immunomodulating diet of 1000 Kcal/day p.o. plus a normal grinded diet that they started on the 5th presurgical day and pursued during the immediate postsurgical period (within the first 24 hours) with EN through a jejunostomy catheter, in a progressive way until reaching 25 kcal/kg/day at days 4-5. EN was kept in place for at least the first 10 days after surgery and laboratory checkups were done before surgery and at days 5 and 10 after surgery. We also performed a prediction equation, with morbidity as the dependent variable and the remaining as independent variables. RESULTS: Sixty-eight patients were studied of whom 36 (35 men and 1 women) suffered from esophageal cancer and 32 (21 men and 11 women) from gastric cancer. Mean age of patients with esophageal cancer was 60 +/- 9.68 years, with a mean postsurgical stay of 36.97 +/- 62.37 days, and for gastric cancer patients mean age was 69.41 +/- 11.53 years and mean stay 24.41 +/- 13.77 days. The comparison of the means of the biochemical nutrition parameters showed a decrease in almost all values at the 5ht post-surgery day in relation to the presurgical determination, and an increase in the measurement at the 10th postsurgical day as compared to the 5th day values. In most of the cases, the differences are statistically significant. For morbimortality prediction, the variables cholesterol, related diseases, CRP, IgM, and male gender, were contributors. CONCLUSIONS: All the analyzed variables, but gender, seem to be appropriate indicators for the study of response to surgical aggression as well as of enteral nutrition. We believe that peri-surgical immunomodulating nutrition recovers the values of postsurgical nutrition parameters. Enteral nutrition through jejunostomy is well tolerated, and has a low and mild morbidity.

Nitric oxide prevents the bacterial translocation and inhibits the systemic inflammatory response produced by implantation of a vascular prosthesis followed by Zymosan A.

OBJECTIVE AND DESIGN: To evaluate the beneficial effects of exogenous NO and its levels of action in a model of SIRS/Bacterial Translocation (BT) induced by two sequential insults. MATERIAL OR SUBJECTS: Eighty-six Wistar rats were submitted to different treatments and their tissue and blood samples were accessed at the end of the experiment. TREATMENT: Nitric Oxide was compared to Gentamicin as the tested guideline for our study. METHODS: Dacron graft implantation (first insult) and subsequent administration of Zymosan A((R)) (second insult) were performed in Wistar rats. The animals were divided into 6 groups: I) No manipulation (BASAL: ); II) Laparotomy (L) + mineral oil (SHAM: ); III) L + Graft-Zymosan (GZ) (CONTROL: ); IV) L + GZ + Antibiotic (A) (ASSAY: I); V) L + GZ + NO (ASSAY: II) and VI) L + GZ + A + NO (ASSAY: III). Determinations: Survival, Bacterial Translocation, myeloperoxidase (MPO), Cytokines (TNF-alpha, IL-1beta, IFN-gamma), Oxygen Free Radical (OFR) SOA and detoxifying enzymes (SOD, Superoxide Dismutase, CAT, Catalase and GPX, Glutathione Peroxidase), Cell Adhesion Molecules, CAMs (ICAM-1, VCAM-1 and PECAM-1) and Nuclear Transcription Factor, NFkappaB. RESULTS: The model established induced a mortality rate of 20% and generated BT in all samples. It also significantly increased all variables, with P < 0.001 for MPO and all Cytokines; P < 0.01 for all OFR, and P < 0.05 for CAMs and for NFkappaB. Treatment with A reduced mortality to 0%, significantly decreased BT, MPO, Cytokines and OFR (P < 0.05), but did not reduce CAMs or NFkappaB. NO, either alone or associated, reduced mortality to 0% and abolished BT, significantly decreasing nearly all the variables studied (P < 0.001 for MPO and all Cytokines; P < 0.01 for OFR, and P < 0.05 for CAMs and for NFkappaB). CONCLUSIONS: The exogenous administration of NO before the two sequential insults prevented BT and controlled SIRS peripherally and at both cellular and transcriptional level in a lasting manner. In contrast, antibiotic treatment only exerted its action at peripheral level. The association of both treatments did not provide any important advantages.

Ruptured aneurysm of the deep femoral artery. Case report and historical review.

The exceptional characteristics of the case are put forward and commented on. The patient was a 96-year-old man with an arteriosclerotic aneurysm of the deep femoral artery, which became urgently apparent on bursting. The surgical resolution was simple and satisfactory. Later investigation showed that the aneurysm was unilateral and only in the deep femoral artery. Deep femoral artery continues to be an exceptional location of true arteriosclerotic aneurysms, above all when they arise in an isolated fashion. However, in recent years the available information has changed two substantial aspects: 1) these peripheral aneurysms have the greatest risk of rupture, and 2) on many occasions it is possible, when the superficial femoral artery is permeable, to give simple and satisfactory treatment (exclusion of the aneurysms without revascularization).

The sialyl Lewis X analogue, CY-1503, down-regulates leucocyte-endothelium interactions and the inflammatory response.

OBJECTIVE: To elucidate mechanisms of protection of ischaemic liver with the sialyl Lewis X analogue CY-1503 by regulation of inflammatory mediators such as oxygen free radicals and cytokines as well as blocking the migration of leucocytes. DESIGN: Laboratory study. SETTING: Teaching hospital, Spain. ANIMALS: 122 male Sprague-Dawley rats divided into four groups: normal (n = 18), sham-operated (n = 28), ischaemic controls (n = 38), and CY-1503 (n = 38). INTERVENTIONS: Warm total hepatic ischaemia for 90 minutes followed by various periods of reperfusion. MAIN OUTCOME MEASURES: Survival, liver histology, liver function, neutrophil infiltration, and free radical and cytokine concentrations. RESULTS: 2/20 ischaemic controls survived, compared with 14/20 given CY-1503. Liver function was better, as was histological appearance judged by the Suzuki score); myeloperoxidase activity was significantly decreased (n = 6 in each group, p<0.01) as were concentrations of free radicals (n = 12 in each group, p<0.05) in the group given CY-1503. CY-1503 had no effect on concentrations of the cytokines tumour necrosis factor-alpha or interleukin 1-alpha. CONCLUSIONS: CY-1503 exerts a protective effect in that it able to down-regulate concentrations of free radicals in our rat model. It is a potent inhibitor of neutrophil migration, but has no effect on cytokine concentrations.

Levels of serum cathepsin L and several glycosidases in patients operated for colorectal cancer.

The activities of several glycosidases and cathepsin L were determined in the blood serum of a control group of ten healthy humans in comparison with a group (group I: 32 subjects) of preoperative colorectal cancer patients (1 week before surgical exeresis) and with another two groups: group II, comprising 18 operated subjects (1 week after surgery), and group III, of 15 operated subjects (4 months after surgery). All subjects were 48-88 years old. Both 'enzyme activity' and 'specific activity' determinations of serum beta-galactosidase, alpha-L-fucosidase and cathepsin L revealed peculiar profiles that differed from one another. Control values differed from those of some stages of the pathological groups, but not of others. These values were compared also with the levels of total, lipid- and glycoprotein-associated serum sialic acid. The usefulness of some assays (especially cathepsin L activity measurement) in the follow-up of the health status of humans operated for colorectal cancer is discussed.

Protective effect of exogenous nitric oxide on the renal function and inflammatory response in a model of ischemia-reperfusion.

BACKGROUND: Tissue subjected to a period of ischemia undergoes morphological and functional damage that increases during the reperfusion phase. The aim of the present work was to assess the possible improvement induced by exogenous administration of nitric oxide (NO) on renal injury and inflammatory reaction in an experimental animal model of renal ischemia-reperfusion (I-R). METHODS: Ischemia was achieved by ligation of the left arteria and vein for 60 min, followed first by contralateral nephrectomy and then reestablishment of blood flow. Molsidomine, used as an NO donor, was administered by systemic injection 30 min before reperfusion. The effect of molsidomine was compared with the effect of hydralazine, a non-NO donor hypotensive agent. RESULTS: Treatment with molsidomine improved the renal dysfunction (increase in plasma creatinine and urea levels) caused by I-R. Moreover, molsidomine blunted the enhanced production of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin [IL] 1alpha), the increase in tissular levels of superoxide anions and oxygen free radical scavengers, and the neutrophilic infiltration observed in the ischemic kidney. One hundred percent survival was achieved in the group of animals treated with the NO donor, whereas the groups of animals undergoing I-R that did not receive molsidomine showed a 40% mortality from the second day after reperfusion. CONCLUSIONS: The present work demonstrated that systemic treatment with an NO donor before reperfusion improved renal function and diminished inflammatory responses in a kidney subjected to an I-R process.

Multicriteria decision analysis for determining drug therapy for intermittent claudication.

Drugs of various classes are prescribed for intermittent claudication. However, there is some discrepancy between medical practice and the scientific basis for drug selection. We have developed a quantitative criteria-based decision analysis to evaluate all implications of drug treatment choices for intermittent claudication. Pentoxifylline, buflomedil, naftidrofuryl and ticlopidine were the drugs selected for analysis. The evaluation criteria were 1) therapeutic efficacy, 2) safety, 3) patient acceptance and 4) cost. A review panel of experts determined the relative importance of each criterion by assigning points (or utility values) to each one. The points were 48, 20, 14 and 18, respectively, for criteria 1, 2, 3 and 4. A probability value, or numerical estimate of how well a drug meets a criterion, was assigned to each drug for each of the 4 criteria. The probability value was multiplied by the utility value to determine the score for each drug and criterion. The criteria points for each drug were added for a total score for the drug. The drug with the highest overall score was pentoxifylline, with 69 points out of an ideal score of 100. The rank order for the other drugs was buflomedil, ticlopidine and naftidrofuryl. A sensitive analysis showed that the relative ranking of the drugs remained unchanged over a series of data modifications.

Tacrolimus (FK506) down-regulates free radical tissue levels, serum cytokines, and neutrophil infiltration after severe liver ischemia.

BACKGROUND: Liver ischemia and reperfusion injury is associated with activation of multiple inflammatory pathways, including free radicals, cytokines, and neutrophil-mediated tissue damage among others. Tacrolimus (FK506) has shown important regulatory effects on some inflammatory pathways, such as cytokines, neutrophils, and adhesion molecules. In this study, we explored a new potential protective mechanism for tacrolimus in the liver inflammatory response after ischemia and reperfusion, specifically its effect on liver tissue free radicals. METHODS: Total hepatic ischemia was produced in the rat for 90 min with an extracorporeal portosystemic shunt. Animals (n=96) were divided into four groups: group 1 comprised normal rats for reference values; group 2 comprised sham operated rats; in group 3, ischemic control rats received only the vehicle; and the experimental treatment group, group 4, received tacrolimus at a dose of 0.3 mg/kg, 4 hr before ischemia. Animal survival was followed up to 7 days. Liver function tests were performed and liver tissue free radicals and myeloperoxidase, serum cytokines (interleukin 1, tumor necrosis factor-alpha), and liver histology were measured 4 hr after reperfusion. RESULTS: Seven-day survival was significantly improved from only 20% in the control group to 55% in the tacrolimus group (P<0.01). Liver function tests, histology, and myeloperoxidase tissue values were significantly improved (P<0.05) with tacrolimus pretreatment. Furthermore, a significant (P<0.05) down-regulation of serum cytokines and liver tissue free radicals was observed. CONCLUSIONS: These data indicate a new and different protective mechanism for FK506 in regard to its ability to down-regulate free radical levels in livers subjected to severe ischemia and reperfusion. Tacrolimus, also confirmed to be a potent suppressor of the cytokine response, specifically interleukin 1 and tumor necrosis, decreased neutrophil tissue migration as well.

Sulfo-Lewis(x) diminishes neutrophil infiltration and free radicals with minimal effect on serum cytokines after liver ischemia and reperfusion.

BACKGROUND: Cell adhesion plays a central role in the pathogenesis of neutrophil-induced hepatic injury after ischemia and reperfusion. Sialyl Lewis(x) binds to selectins mediating neutrophil adherence to endothelium, thereby facilitating subsequent migration and tissue damage. AIM: We studied the effect of a novel sulfo-derivative of sialyl Lewis(x), GM-1998, on the liver inflammatory response after ischemia and reperfusion. Specifically, we evaluated its impact on three key inflammatory mediators: neutrophil migration, free radicals, and serum cytokines. MATERIAL AND METHODS: Rats were subjected to total hepatic ischemia for 90 min using an extracorporeal portosystemic shunt to avoid splanchnic congestion. GM-1998 was given at a total dose of 20 mg/kg both prior to and after reperfusion. Liver function tests, liver tissue free radicals, and myeloperoxidase (MPO), serum cytokines (IL-1, TNF-alpha), and liver histology were analyzed 4 hr after reperfusion. Additionally, survival was followed for up to 7 days. RESULTS: Seven-day survival significantly increased from 20% in the control group to 65% in the sulfo-Lewis(x) treated group. Liver function tests and histological damage scores were improved in comparison to controls. We observed significant downregulation of free radicals and neutrophil migration. This compound did not significantly affect serum cytokine levels. CONCLUSIONS: GM-1998 showed a protective effect in an in vivo model of severe liver ischemia and reperfusion by decreasing tissue free radical levels and selectin-mediated neutrophil migration. This protective effect was also reflected in improved liver function tests and histological response leading to better survival. We confirmed the beneficial effect of neutrophil blockade as a key target to prevent damage after the reperfusion phenomenon by using a glycomimetic sulfo-Lewis(x).

[Perfusion of donor tissue improves the preservation of graft in heterotopic tracheal transplantation]. / La perfusión tisular del donante mejora la conservación del injerto en el transplante traqueal heterotópico.

To assess the effect on tracheal graft preservation of perfusion of donor tissue with a Collins solution before extraction and immunosuppression of the recipient. An experimental study was performed in 36 albino rabbits with revascularized heterotopic cervical reconstruction of the trachea with omentum. The animals were distributed in four groups. Groups I (n = 9) and III (n = 9) were transplanted with non perfused donor tissue. Animals in groups II (n = 9) and IV (n = 9) received grafts perfused with Collins solution. Immunosuppression with steroids and cyclosporin was continued for 21 days in groups III and IV. In a mid portion of the trachea viewed under optical microscope, the degree of inflammation or circumferential necrosis was assessed on a scale of 0 to 9 by adding the scores for mucosa, submucosa and cartilage. The mean score for tracheal lesion was lower in group IV, with a likelihood of random difference of less than 5%. Perfusion of peritracheal tissues with Collins solution in the donor, in addition to immunosuppression decreases the extent of tissue damage in the tracheal graft.

[Nutrition and bacterial translocation]. / Nutrición y translocación bacteriana.

The present work is part of a presentation given at the Scientific Meeting of the Association for Surgical Nutrition and Metabolism, during the XX National Congress for Surgery (Madrid, November 1994). The authors, prior to presenting their experiences, define and high light the importance of the phenomenon of "Bacterial Translocation" (BT). Afterwards, and based on several experimental studies performed by them, they attempt to answer two questions: 1) Is the term BT correct? 2) Is BT a physiological or a pathological state? Finally they review the relationship which exists between bacterial translocation and nutrition, both from a causative point of view as from the prevention and therapy of the same.

Flow cytometry in the diagnosis of cancer.

Flow cytometry has rapidly expanded from basic research to clinical laboratories mainly due to its unique characteristics regarding cell analysis. Among the clinical uses of flow cytometry cancer represents one of the most relevant. Several applications of flow cytometry can currently be applied to the study of cancer, including the detection of tumour cell DNA aneuploidy, the analysis of tumour cell proliferation and the immunophenotyping of leukemias. Although standardized flow cytometry protocols for these applications are scanty, the clinical value has been clearly established. The presence of DNA aneuploidy and a high proportion of S-phase tumour cells have been associated with tumour malignancy and a poor prognosis. The immunophenotype of leukaemia is of great help both for the diagnosis and classification of chronic lymphoproliferative disorders and acute leukaemias, especially in acute lymphoblastic leukemia cases and the M0, M3-variant, M6 and M7 acute myeloblastic leukaemia subtypes. In addition, it allows the identification of relatively rare leukemia cases such as the biphenotypic and the Nk-cell lineage leukemias. The development of flow cytometry is continuously bringing new applications into the clinical laboratory in the area of cancer diagnosis.

Double-blind, controlled, multicenter study of indobufen versus placebo in patients with intermittent claudication.

The objective of the study was to evaluate the efficacy and safety of indobufen compared with placebo in the treatment of moderately severe intermittent claudication. The study consisted of a four-week single-blind, placebo-controlled run-in phase, followed by a six-month double-blind randomized treatment period. A total of 302 patients were allocated to treatment with either placebo (154 patients) or indobufen (148) 200 mg twice daily. The results of the overall intention-to-treat analysis of the study population showed statistically significant superiority of indobufen over placebo after six months for both the initial (ICD) and absolute claudication distances (ACD). The ICD before treatment with indobufen or placebo averaged 137.9 +/- 68.2 and 136.6 +/- 63.2 m (mean +/- SD), respectively. After six months' treatment with active drug or placebo, this parameter reached 227.9 +/- 174.4 and 153.1 +/- 86.8 m (mean +/- SD), respectively (p < 0.01). Similar results were obtained on ACD. The reduction of lower limb symptoms also suggested a greater clinical benefit in the indobufen-treated patients. There was no significant change in either group in the ankle/arm pressure ratio at the end of treatment. Adverse events of any type were reported by 18 patients (12.2%) in the indobufen group and by 11 patients (7.2%) in the placebo group. The mechanism whereby the drug is effective in this clinical condition could be related to both its antiplatelet and hemorheologic effects.

[An experimental model of bacterial translocation]. / Modelo experimental sobre translocación bacteriana.

The authors submit an experimental model for bacterial translocation (administering OF-1 mice Zymosan intra-peritoneally at a dose of 1 mg/kg weight). The existence is confirmed of this new mechanism of infection (0% of translocation in control groups, as against 80% in the trial group -p < 0.001). The bacteria in the translocated organs coincide with those present in the fecal flora of the experimental animal. This study is the point of departure for subsequent research to study the physiopathological mechanisms of the phenomenon, which will enable us subsequently to reach better preventive and/or therapeutic decisions.

[Pseudomembranous colitis after surgery for a ruptured abdominal aortic aneurysm]. / Colitis pseudomembranosa después de cirugía por aneurisma aórtico abdominal roto.

We present a rare postoperative complication after surgical procedures for rupture of abdominal aortic aneurysms. The disease, a pseudomembranous colitis, was early recognized (by evidence of clostridium difficile after a coprocultive) and satisfactorily treated with vancomycin. From the literature review we found only a similar case but results were absolutely different from our case.