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Background: To assess the relationship between hospital volume and early postoperative outcome the incidence and early outcome of all esophagectomies, pancreaticoduodenectomies and gastric resections in Denmark from 1996 to 2004 was described., Methods: The National Patient Registry and discharge information from all hospital departments were analysed for all the operations due to a malignant diagnosis. All information was examined for postoperative length of stay and hospital mortality., Results: During the study period 26 departments performed at least one esophageal resection, 13 departments performed at least one Whipple procedure and 37 departments performed at least one gastric resection. Four departments performed more than 20 esophageal resections per year, whereas one department performed more than 20 Whipple procedures and one more than 20 gastric resections per year. The overall mean length of stay was 21.6 days, 24 days and 18 days for esophageal, pancreatic and gastric resections, respectively, with no difference between high and low volume departments. The hospital mortality was 8.6%, 8.9% and 8.2%, respectively., Conclusion: The overall high mortality and long postoperative stay in patients undergoing upper gastrointestinal cancer surgery in Denmark calls for improvement by regionalisation into 3-4 departments and monitoring of results.

Polyamine toxins, such as philanthotoxins, are low-molecular-weight compounds isolated from spiders and wasps, which modulate ligand-gated ion channels in the nervous system. Philanthotoxins bind to the pore-forming region of AMPA receptors, a subtype of glutamate receptors which are important for memory formation and are involved in neurodegenerative diseases. Previous studies have demonstrated that modification of the polyamine moiety of philanthotoxins can lead to very potent and highly selective ligands for the AMPA receptor, as exemplified with philanthotoxin-56. Much less attention has been paid to the importance of the aromatic head group of philanthotoxins, but herein we demonstrate that modification of this moiety leads to a significant improvement in potency relative to philanthotoxin-56 at cloned AMPA receptors. Interestingly, the incorporation of an adamantane moiety is particularly favorable, and the most potent compound has a Ki value of 2 nM, making it the most potent uncompetitive antagonist of AMPA receptors described to date. Such compounds are potentially useful as neuroprotective agents.

A model capable of quantifying the potential environmental impacts of agricultural application of composted or anaerobically digested source-separated organic municipal solid waste (MSW) is presented. In addition to the direct impacts, the model accounts for savings by avoiding the production and use of commercial fertilizers. The model is part of a larger model, Environmental Assessment of Solid Waste Systems and Technology (EASEWASTE), developed as a decision-support model, focusing on assessment of alternative waste management options. The environmental impacts of the land application of processed organic waste are quantified by emission coefficients referring to the composition of the processed waste and related to specific crop rotation as well as soil type. The model contains several default parameters based on literature data, field experiments and modelling by the agro-ecosystem model, Daisy. All data can be modified by the user allowing application of the model to other situations. A case study including four scenarios was performed to illustrate the use of the model. One tonne of nitrogen in composted and anaerobically digested MSW was applied as fertilizer to loamy and sandy soil at a plant farm in western Denmark. Application of the processed organic waste mainly affected the environmental impact categories global warming (0.4-0.7 PE), acidification (-0.06 (saving)-1.6 PE), nutrient enrichment (-1.0 (saving)-3.1 PE), and toxicity. The main contributors to these categories were nitrous oxide formation (global warming), ammonia volatilization (acidification and nutrient enrichment), nitrate losses (nutrient enrichment and groundwater contamination), and heavy metal input to soil (toxicity potentials). The local agricultural conditions as well as the composition of the processed MSW showed large influence on the environmental impacts. A range of benefits, mainly related to improved soil quality from long-term application of the processed organic waste, could not be generally quantified with respect to the chosen life cycle assessment impact categories and were therefore not included in the model. These effects should be considered in conjunction with the results of the life cycle assessment.

This study investigated the long-term survival rate of 589 patients enrolled in a trial in 1992-1995 who underwent colorectal surgery. The patients were randomised to receive leucocyte-depleted or buffy-coat-poor blood when transfusion was indicated. Significantly more of the non-transfused patients (59%) were alive seven years later compared to patients transfused with leucocyte-depleted blood (41%) and to patients transfused with buffy-coat-poor blood (45%).

Polyamines and polyamine toxins are biologically important molecules, having modulatory effects on nucleotides and proteins. The wasp toxin, philanthotoxin-433 (PhTX-433), is a non-selective and uncompetitive antagonist of ionotropic receptors, such as ionotropic glutamate receptors and nicotinic acetylcholine receptors. Polyamine toxins are used for the characterization of subtypes of ionotropic glutamate receptors, the Ca2+-permeable AMPA and kainate receptors. A derivative of the native polyamine toxin, philanthotoxin-56 (PhTX-56), has recently been shown to be an exceptionally potent and selective antagonist of Ca2+-permeable AMPA receptors. PhTX-56 and its labeled derivatives are promising tools for structure-function studies of the ion channel of the AMPA receptor. We now describe the design and synthesis of 3H-, 13C-, and 15N-labeled derivatives of PhTX-56 for molecular level studies of AMPA receptors. [3H]PhTX-56 was prepared from a diiodo-precursor with high specific radioactivity, providing the first radiolabeled ligand binding to the pore-forming part of AMPA receptors. For advanced biological NMR studies, 13C and 15N-labeled PhTX-56 were synthesized using solid-phase synthesis. These analogs can provide detailed information on the ligand-receptor interaction. In conclusion, synthesis of labeled derivatives of PhTX-56 provides important tools for future studies of the pore-forming region of AMPA receptors.

Introduction: We evaluated the organisation, management and outcome for patients operated on with gastric resection for cancer in Denmark in the period 1999-2003., Materials and Methods: Nationwide data based on the National Patient Registry and discharge information from hospital departments in the period 1 January 1999 to 31 December 2003 were analysed., Results: Thirty-seven departments performed 537 resections, with an average of 20 departments per year performing such operations. Five departments performed 57.2% of the operations, while 20 departments performed 10.2%. The average postoperative stay was 18 days and the hospital mortality rate was 8.2%, equally distributed with 7.8% for Billroth II resections and 8.5% for total gastrectomy., Discussion: The organization of gastric cancer surgery in Denmark in 1999-2003 was not optimal, with about 20 departments performing about 100 gastric resections annually, and with a mortality rate of slightly over 8% and an average hospital stay of 18 days. We propose that in future, gastric resections for cancer should be performed in a maximum of five departments nationwide.

Lifestyle interventions including exercise programs are cornerstones in the prevention of obesity-related diabetes. The AMP-activated protein kinase (AMPK) has been proposed to be responsible for many of the beneficial effects of exercise on glucose and lipid metabolism. The effects of long-term exercise training or 5-aminoimidazole-4-carboxamide-1-beta-d-riboruranoside (AICAR) treatment, both known AMPK activators, on the development of diabetes in male Zucker diabetic fatty (ZDF) rats were examined. Five-week-old, pre-diabetic ZDF rats underwent daily treadmill running or AICAR treatment over an 8-week period and were compared with an untreated group. In contrast to the untreated, both the exercised and AICAR-treated rats did not develop hyperglycemia during the intervention period. Whole-body insulin sensitivity, as assessed by a hyperinsulinemic-euglycemic clamp at the end of the intervention period, was markedly increased in the exercised and AICAR-treated animals compared with the untreated ZDF rats (P < 0.01). In addition, pancreatic beta-cell morphology was almost normal in the exercised and AICAR-treated animals, indicating that chronic AMPK activation in vivo might preserve beta-cell function. Our results suggest that activation of AMPK may represent a therapeutic approach to improve insulin action and prevent a decrease in beta-cell function associated with type 2 diabetes.

Polyamine toxins, isolated from spiders and wasps, have been used as pharmacological tools for the study of ionotropic receptors, but their use have so far been hampered by their lack of selectivity. In this mini-review, we describe how careful synthetic modification of native polyamine toxins have led to highly selective and potent new ligands for specific ionotropic receptors, particularly certain glutamate receptors subtypes, as well as nicotinic acetylcholine receptors. Moreover, the recent developments of synthetic methods, that have greatly facilitated the synthesis of polyamine toxins and their analogues are described.

We have previously described a series of competitive GABA(A) antagonists derived from the low-efficacy partial agonist 5-(4-piperidyl)-3-isoxazolol (4-PIOL, 4). The 2-naphthylmethyl analogue, 4-(2-naphthylmethyl)-5-(4-piperidyl)-3-isoxazolol (5), provided affinity for the GABA(A) receptor site higher than that of the standard GABA(A) receptor antagonist, SR 95531 (3). Molecular modeling studies of these compounds exposed a cavity at the receptor recognition site capable of accommodating aromatic groups of substantial size in the 4-position in the 3-isoxazolol ring. Here we present a series of analogues of 5, with various substituents in different positions in the naphthyl ring system (6a-k), and compounds with aromatic substituents directly attached to the 4-position of the 3-isoxazolol ring (7l-n). The compounds have been pharmacologically characterized using receptor-binding assays and electrophysiological whole-cell patch-clamp techniques. All of the tested compounds show affinity for the GABA(A) receptor site. While the 5-, 7-, and 8-bromo analogues, 6b-d, showed receptor affinities (K(i) = 45, 109, and 80 nM, respectively) comparable with that of 5 (K(i) = 49 nM), the 1-bromo analogue, 6a, provided the highest receptor affinity of the series (K(i) = 10 nM). Introduction of a series of different substituents in the 1-position in the 2-naphthyl ring system led to compounds, 6e-k, with retained high affinity for the GABA(A) receptor (K(i) = 16-250 nM). Introduction of a phenyl ring directly into the 4-position on the 3-isoxazolol ring gave a 41-fold increase in affinity relative to that of 4-PIOL. In whole-cell patch-clamp recordings from cultured cerebral cortical neurons, all of the tested compounds were able to inhibit the effect of the specific GABA(A) agonist isoguvacine, 6a showing antagonist potency (IC(50) = 42 nM) markedly higher than that of 3 (IC(50) = 240 nM). Molecular modeling studies, based on the compounds described, emphasized the importance of the distal ring in 5 for receptor affinity and the considerable dimensions of the proposed receptor cavity. Furthermore, the phenyl rings in 7l and in 6k were shown to represent highly favorable positions for an aromatic ring in previously unexplored receptor regions in terms of a pharmacophore model.

Aims: To assess the postoperative morbidity and mortality, length of stay and long-term survival after resection of carcinoma of the oesophagus and gastro-oesophageal junction, after establishment of a new surgical team unit between thoracic and gastroenterologic surgeons., Methods: We analysed the prospective collected data of 166 consecutive patients who underwent a transthoracic oesophageal resection between June 1997 and December 2003., Results: There were 119 men and 47 women. The median age was 63 years (range 36-81). Fifty-five patients (33%) had squamous cell carcinoma and 111 (67%) had adenocarcinoma. Postoperative complications occurred in a total of 60 patients (36%). Ten patients (6%) died postoperatively, eight (4.8%) due to medical and two (1.2 %) due to surgical complications. The median postoperative length of stay was 11 days (range 6-75). The overall 3- and 5- years survival was 35.6% and 30.6% respectively. Survival was adversely affected by patient age and tumor stage., Conclusions: Concentrating resection for carcinoma of the oesophagus and oesophagogastric junction to a dedicated team of specialists, including both gastrointestinal and thoracic surgeons as well as thoracic-anaesthesiological know-how, results in acceptable complication rates as well as low mortality rates especially due to surgical complications.

Prolonged growth hormone (GH) excess is known to be associated with insulin resistance, but the underlying mechanisms remain unknown. The aim of this study was to assess the impact of GH on insulin-stimulated glucose metabolism and insulin signaling in human skeletal muscle. In a cross-over design, eight healthy male subjects (age 26.0 +/- 0.8 yr and body mass index 24.1 +/- 0.5 kg/m2) were infused for 360 min with either GH (Norditropin, 45 ng.kg(-1).min(-1)) or saline. During the final 180 min of the infusion, a hyperinsulinemic euglycemic clamp was performed (insulin infusion rate: 1.2 mU.kg(-1).min(-1)). Muscle biopsies from vastus lateralis were taken before GH/saline administration and after 60 min of hyperinsulinemia. GLUT4 content and insulin signaling, as assessed by insulin receptor substrate (IRS)-1-associated phosphatidylinositol 3-kinase and Akt activity were determined. GH levels increased to a mean (+/-SE) level of 20.0 +/- 2.3 vs. 0.5 +/- 0.2 microg/l after saline infusion (P < 0.01). During GH infusion, the glucose infusion rate during hyperinsulinemia was reduced by 38% (P < 0.01). In both conditions, free fatty acids were markedly suppressed during hyperinsulinemia. Despite skeletal muscle insulin resistance, insulin still induced a similar approximately 3-fold rise in IRS-1-associated PI 3-kinase activity (269 +/- 105 and 311 +/- 71% compared with baseline, GH vs. saline). GH infusion did not change Akt protein expression, and insulin caused an approximately 13-fold increase in Akt activity (1,309 +/- 327 and 1,287 +/- 173%) after both GH and saline infusion. No difference in total GLUT4 content was noted (114.7 +/- 7.4 and 107.6 +/- 16.7 arbitrary units, GH vs. saline, compared with baseline). In conclusion, insulin resistance in skeletal muscle induced by short-term GH administration is not associated with detectable changes in the upstream insulin-signaling cascade or reduction in total GLUT4. Yet unknown mechanisms in insulin signaling downstream of Akt may be responsible.

Radiocarbon measurements have been used in combination with "bomb 14C" models to estimate turnover of soil organic carbon fractions. However, the bomb 14C models assume that all SOC fractions are formed directly from external inputs of carbon, which is not always valid because some SOC fractions may receive carbon from other SOC fractions. Due to the continuous inputs of organic carbon, we argue that the most appropriate way to describe the age of SOC is by an age distribution. We developed age distributed models of SOC fractions and derived analytical solutions to them. The models all assume that SOC fraction decay can be described by first-order kinetics, but differ in their assumptions about the pathway of SOC fraction formation. The solutions can be used to estimate age distributions at steady state of different SOC fractions based on their radiocarbon content. These age distributions can be used to calculate the mean age, mean residence time, and other vital statistics of each measurable SOC fraction. Furthermore, if a sequential scheme is used to isolate the SOC fractions, an estimated age distribution of the total SOC can be obtained by adding the contributions of each soil fraction. The age distributions can be very helpful in interpretations of soil organic carbon dynamics in different soils.

We developed evidence-based recommendations for the minimisation of errors in intravenous drug administration in anaesthesia from a systematic review of the literature that identified 98 relevant references (14 with experimental designs or incident reports and 19 with reports of cases or case series). We validated the recommendations using reports of drug errors collected in a previous study. One general and five specific strong recommendations were generated: systematic countermeasures should be used to decrease the number of drug administration errors in anaesthesia; the label on any drug ampoule or syringe should be read carefully before a drug is drawn up or injected; the legibility and contents of labels on ampoules and syringes should be optimised according to agreed standards; syringes should (almost) always be labelled; formal organisation of drug drawers and workspaces should be used; labels should be checked with a second person or a device before a drug is drawn up or administered.

A range of analytical methods exist for the determination of paracetamol in biological fluids. However, to understand the fate of paracetamol and the effect of other drugs on its disposition in vivo, the major metabolites require quantification in urine and plasma. A method to simultaneously quantify paracetamol, paracetamol glucuronide (PG) and paracetamol sulphate (PS) in plasma and urine with superior sensitivity is therefore desired, especially if the volume of plasma available is low. A simple isocratic reverse phase high-performance liquid chromatography (HPLC) assay with spectrophotometric detection has been developed. The method, requiring only 100 microl of plasma and 50 microl of urine, utilizes a reversed-phase C18 column, a wavelength of 254 nm for detection and a mobile phase composed of potassium dihydrogen orthophosphate (0.1 M)-isopropanol-tetrahydrofuran (THF) (100:1.5:0.1, v/v/v) adjusted to pH 3.7 with phosphoric acid. The method is sensitive and linear in plasma within a concentration range from 0.4 to 200 microM for paracetamol, PG and PS. For PG and PS in urine, the method is sensitive and linear within a concentration range from 100 to 20,000 microM. Over these ranges, accuracy and precision were less than 12%. The assay has been used to measure concentrations of paracetamol and the two metabolites in plasma collected by finger-prick sampling and of the metabolites in urine from healthy volunteers administered a single oral dose of 1000 mg of paracetamol.

Physical activity is known to increase insulin action in skeletal muscle, and data have indicated that 5'-AMP-activated protein kinase (AMPK) is involved in the molecular mechanisms behind this beneficial effect. 5-Aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) can be used as a pharmacological tool to repetitively activate AMPK, and the objective of this study was to explore whether the increase in insulin-stimulated glucose uptake after either long-term exercise or chronic AICAR administration was followed by fiber-type-specific changes in insulin signaling and/or changes in GLUT-4 expression. Wistar rats were allocated into three groups: an exercise group trained on treadmill for 5 days, an AICAR group exposed to daily subcutaneous injections of AICAR, and a sedentary control group. AMPK activity, insulin-stimulated glucose transport, insulin signaling, and GLUT-4 expression were determined in muscles characterized by different fiber type compositions. Both exercised and AICAR-injected animals displayed a fiber-type-specific increase in glucose transport with the most marked increase in muscles with a high content of type IIb fibers. This increase was accompanied by a concomitant increase in GLUT-4 expression. Insulin signaling as assessed by phosphatidylinositol 3-kinase and PKB/Akt activity was enhanced only after AICAR administration and in a non-fiber-type-specific manner. In conclusion, chronic AICAR administration and long-term exercise both improve insulin-stimulated glucose transport in skeletal muscle in a fiber-type-specific way, and this is associated with an increase in GLUT-4 content.

The distribution of ptaquiloside (PTA) was studied in four Danish bracken populations in order to evaluate the transfer of PTA from ferns to soil. Populations showed statistically significant differences in PTA contents of fronds and rhizomes despite large in-site variations. The highest concentrations were encountered in fronds with concentrations ranging between 213 and 2145 microg/g, while rhizomes had concentrations between 11 and 902 microg/g. PTA was present in soil materials in amounts of 0.22-8.49 microg/g but apparently with no correlation with PTA contents of fronds or rhizomes. Laboratory tests showed that water could leach PTA from bracken fronds, which is in support of the high soil contents observed at sites exposed to heavy showers just before sampling. The observed soil contents correspond to estimated soil solution concentrations of 200-8500 microg/liter, demonstrating a substantial risk of PTA contamination of surface water and groundwater.

Introduction: We evaluated the changes in Denmark since the 1980s in the incidence, management and outcome of oesophageal resections., Material and Methods: The national patient hospital register and discharge information from the hospitals were examined for the number of oesophageal resections performed, the length of the postoperative stay, readmission, postoperative complications, and hospital mortality in the period 1/1-1997 to 30/6-2000., Results: Twenty-six departments in 18 hospitals performed 476 resections. Five hospitals accounted for 92% of all the resections performed. In three hospitals, the resections were carried out in three different departments and 18 departments performed fewer than four resections per year. The postoperative stay was 19.2 days. The frequency of surgical complications was 19% and hospital mortality was 10.7%., Discussion: The small number of oesophageal resections performed in many departments in Denmark is not in accordance with international recommendations, which say that the operation should be performed in high volume centres by experienced oesophageal surgeons, including thoracic surgeons, surgical gastroenterologists, and thoracic anaesthesiologists. On these results, it is recommended that the operation is performed in few centres and by few surgeons in multidisciplinary teams.

Objectives: In the University Department of Surgical Gastroenterology, Arhus University Hospital, the frequency of complications to acute and elective cholecystectomy was investigated before and after introduction of laparoscopic cholecystectomy., Material and Methods: A retrospective survey turned up 1768 patients in the period of conventional open surgery (1974-1985) and 1432 patients in the laparoscopic period (1991-1998). All patients with exploration of the common bile duct were excluded., Results: In the open period 12 patients (0.68%) had lesions of the common bile duct requiring reconstruction. In patients operated on with laparoscopic cholecystectomy, lesions of the common bile duct were found in three patients (0.21%) (p = 0.06). Lesions of the cystic duct or an aberrant bile duct occurred in 14 patients (0.79%) during the open period and in 24 patients (1.7%) (p < 0.05) operated on with the laparoscopic technique. Infectious and cardiopulmonary complications were seen in significantly more patients operated on with the open technique., Discussion: It is concluded that laparoscopic cholecystectomy offers a safe procedure, although the technique can still be improved, especially with respect to decreasing leakage from the cystic duct.

Open (OC) or laparoscopic (LC) cholecystectomy is considered a relative contraindication in patients with liver cirrhosis. The effect of LC and OC on the hepatic catabolic stress response was studied in patients with postnecrotic liver cirrhosis and chronic hepatitis to define the most suitable procedure from a metabolic point of view. Altogether 14 patients with cirrhosis and 14 with chronic hepatitis were randomized to LC or OC (n = 7 in each group). The increase in the functional hepatic nitrogen clearance (FHNC) was quantified. Changes in glucose, insulin, glucagon, cortisol, epinephrine, norepinephrine, and prostaglandin E(2) (PGE(2)) were observed. There was no difference in FHNC between LC and OC in any of the patients. Among cirrhotic patients OC caused a 132% increase in FHNC (p < 0.05) and among the hepatitis patients a 69% increase (p < 0.05). In contrast, there was no significant increase following LC in any of the patients. OC increased fasting glucose and insulin in the hepatitis patients (p < 0.01 and p < 0.001, respectively) and in the cirrhosis group (p < 0.01 and p < 0.05, respectively). Alanine stimulation increased glucose in hepatitis patients after OC (p < 0.05) and after LC (p < 0.01). Stimulated glucagon increased after OC in the hepatitis group (p < 0.05). During stimulation cortisol was higher following LC in hepatitis patients (p < 0.01) and cirrhotic patients (p < 0.05). Fasting PGE(2) was down-regulated after LC in hepatitis patients (p < 0.05) and cirrhotic patients (p < 0.01) and after OC in the hepatitis group (p < 0.001). FHNC is similar after LC and OC. Thus from a metabolic point of view, LC has no advantage over OC.

Background: As impaired immune function observed in cirrhotic patients is known to increase the risk of postoperative complications, the immunological response to surgery was investigated., Methods: Twenty-eight patients with postnecrotic liver cirrhosis or chronic hepatitis C and symptomatic gallstone disease were randomly allocated to laparoscopic (LC) or open cholecystectomy (OC). Changes in concentrations of cytokines (TNF-alpha, IL-1beta, IL-6, IL-8 and IL-10) were followed and the effect of surgical trauma on the distribution of lymphocyte subpopulations (CD3, CD4, CD8, CD16 and CD19) and NK cell cytotoxicity were measured., Results: After OC a decrease in circulating CD3 (p < 0.05) and CD4 (p < 0.05) and an increase in CD19 (p < 0.05) cells were detected in contrast to LC after which only CD16 cells decreased (p = 0.05). The number of CD3 cells was higher after LC than after OC (p < 0.01), whereas the number of CD19 cells was higher after OC than after LC (p < 0.01). NK cell cytotoxicity was reduced after LC (p < 0.05). In cirrhotic patients circulating cytokines were unaffected by OC, whereas TNF-alpha (p < 0.05) and IL-1beta (p < 0.05) were reduced after LC. In chronic hepatitis IL-1beta decreased after OC (p = 0.05) and IL-10 was significantly higher after LC than following OC (p < 0.05)., Conclusion: The immune response is less pronounced after a laparoscopic procedure compared to a conventional approach in patients with chronic liver disease.

From a surgical point of view, one of the most important consequences of blood transfusion is the immunosuppressive effect and its possible link to postoperative infectious complications and cancer recurrence. The underlying mechanism of transfusion-induced immunosuppression seems to be mediated by transfusion with leukocytes. In prospective randomized trials, therefore, efforts have been made to control the immunosuppressive effect of allogeneic blood transfusion by the use of leukocyte-reduced blood. Only one prospective clinical trial has asserted the effect of leukocyte reduction on cancer recurrence, and no benefit to outcome was found. In four big randomized, prospective clinical trials, allogeneic blood transfusion was associated with significantly increased rates of postoperative infections, and the use of leukocyte reduction was found to have striking benefits in three of the trials, with a several-fold reduction in rates of morbidity and mortality.

Objective and Design: To study the potential effect of ranitidine on postoperative infectious complications following emergency colorectal surgery. A randomized, placebo-controlled, double-blind trial was carried out in three university clinics and two county hospitals in Denmark., Patients and Treatment: One hundred and ninety-four consecutive patients undergoing acute colorectal surgery for perforated and/or obstructed large bowel were randomized in a double-blind fashion to receive ranitidine 100 mg i.v. twice a day commencing at induction of anesthesia and continued for five days (group I) or i.v. placebo (group II). All patients were given 1.5 g metronidazole plus 3.0 g cefuroxime at the time of surgery. Patients with perforation of the colon or rectum were given metronidazole and cefuroxime for further 3 days. All patients were assessed daily until discharge from the hospital. Thirty patients were withdrawn from the study (for reasons such as other diagnosis, refused to continue, medication not given as prescribed)., Main Outcome Measures: Patients were observed for signs of infectious complications; such as wound infection, intra-abdominal abscess, septicemia, and pneumonia., Results: Both groups were similar with respect to age, sex, weight, duration of surgery, blood transfusions, and site of the procedure, as well as the histologic nature of the underlying disease process. However, the Mannheim Peritonitis Index (MPI) was significantly higher in group I compared with group II (p < 0.05). Wound infection, intraabdominal abscess, septicemia, and pneumonia were 12.9%, 5.2%, 3.8% and 14%, respectively in group I. In group II, the infectious complications were 16.1%, 6.8%, 6.9% and 22%, respectively. Twelve patients (13.8%) in the placebo group developed more than one complication compared with 5 patients (6.5%) in the ranitidine group., Conclusion: Ranitidine may have a beneficial effect on postoperative infectious complications in patients following acute colorectal surgery.

The objective of the study was to investigate certain immune parameters in patients undergoing elective colorectal surgery and receiving either whole blood transfusion or leucocyte-filtrated blood. Sixty consecutive patients were randomly allocated to receive either whole blood transfusion or leucocyte-filtrated blood leucocyte when transfusion was indicated. The immune parameters were investigated on the day of surgery and on day 3, 7 and 30 postoperatively. Transfusion with whole blood was followed by a significant decrease in lymphocyte proliferation and CD4+/CD8+ ratio (p < 0.01) as well as a significant increase in soluble interleukin-2 receptor and interleukin-6 (p < 0.01). Furthermore transfusion with whole blood was accompanied by a significant increase in postoperative infectious complications (p < 0.01). Patients transfused with leucocyte-filtrated blood had only minor and passing changes in the immune parameters and developed no infectious complications, indicating that effective leucocyte filtration abolishes transfusion-associated immunosuppression.

Background: Allogeneic blood transfusion is associated with an increased frequency of postoperative infection. We studied whether such events can be avoided by the intraoperative and postoperative use of leucocyte-depleted blood., Methods: 589 consecutive patients scheduled for elective colorectal surgery were randomised to receive buffy-coat poor (n = 299) or filtered leucocyte-depleted red-cells (n = 290) when transfusion was indicated. 260 patients actually received blood transfusion. Three patients were excluded from analysis., Findings: The 142 patients randomised to and transfused with buffy-coat-poor blood had a significantly higher frequency of wound infections and intra-abdominal abscesses than the 155 patients who were allocated to this group but who were not transfused. (12 vs 1%, p < 0.0001) and (5 vs 0%, p = 0.005), respectively. Those receiving buffy-coat-poor blood also had a significantly higher frequency of wound infections and intra-abdominal abscesses than the 118 randomised to and receiving leucocyte-depleted blood (12 vs 0%, p < 0.0001) and (5 vs 0%, p = 0.017), respectively. Postoperative pneumonia occurred at a significantly higher rate in patients receiving buffy-coat-poor blood: 23 versus 3% in non-transfused patients (p < 0.0001), and 23 versus 3% in patients transfused with leucocyte-depleted blood (p < 0.001). The mortality rate between the groups was not statistically different., Interpretation: Our data suggests that the association between allogeneic blood transfusion and postoperative infection is limited to allogeneic blood products that are not adequately depleted of immunosuppressive leucocytes. This undesirable effect can be reduced by leucocyte depletion with high-efficiency filters.

In a randomized study the effect of whole blood transfusion versus bedside leucocyte-depleted blood transfusion on lymphocyte proliferation, CD4+:CD8+ ratio, and levels of soluble interleukin 2 receptor (sIL-2R) and interleukin (IL) 6, as well as on the development of postoperative wound infection and intra-abdominal abscess, was assessed in 60 patients undergoing elective colorectal surgery. Transfusion with whole blood induced a significant decrease in lymphocyte proliferation and CD4+ :CD8+ ratio (P < 0.01) as well as a significant increase in sIL-2R and IL-6 levels (P < 0.01). Furthermore, transfusion with whole blood was accompanied by a significant increase in postoperative infectious complications (P < 0.01). In patients transfused with leucocyte-depleted blood only slight and transient changes were observed, which were not significantly different from those observed in non-transfused patients.

Background: The Danish contribution to evaluation and treatment of bleeding oesophageal varices., Methods: Danish papers dealing with portal hypertension and oesophageal varices have been reviewed and set in relation to international publications., Results: The Danish papers have mainly contributed with controlled clinical trials concerning both primary and secondary prophylaxis. Furthermore, they have dealt with pathophysiologic, clinical and experimental studies concerning portal haemodynamics and the evolution and treatment of variceal bleeding., Conclusion: The Danish studies have been well designed and are frequently cited. Further prospective randomized studies in the new treatment modalities are encouraged.

1. From two independent experimental studies conducted in 48 minipigs with oesophageal sclerotherapy and concomitant treatment with epidermal growth factor, blood samples together with bone marrow biopsies were analysed for safety data. 2. Four to five weeks of systemic treatment with epidermal growth factor induced a decline in blood haemoglobin concentration in a time- and dose-dependent and reversible manner but without an effect on leucocyte or platelet counts. 3. The bone marrow expressed decreased amounts of haematopoietic tissue and reduced numbers of erythropoietic cells. 4. Four to five weeks of systemic treatment with epidermal growth factor induced reversible increases in serum concentrations of creatinine and urea, most likely reflecting renal impairment. 5. Groups in which creatinine and urea were not increased also had reduced blood haemoglobin concentrations. 6. These findings suggest that epidermal growth factor selectively impaired the erythropoiesis and stress the importance of risk-benefit analysis concerning the potential therapeutic applications of epidermal growth factor.

Objective: To investigate the role of epidermal growth factor (EGF), a small (relative molecular mass 6000) polypeptide with mitogenic properties in the protection of gastrointestinal mucosal integrity., Design: A prospective, randomized and blinded study., Methods: Twenty-four minipigs with surgically induced portal hypertension underwent four consecutive weekly sessions of oesophageal sclerotherapy with 5 ml 1% polidocanol and were concomitantly treated with either a placebo or human recombinant EGF administered subcutaneously. Mucosal damage was evaluated on a weekly basis by endoscopic estimation of the size of the ulcerated area and by post-mortem morphometry. The EGF-induced morphological changes in the oesophageal epithelium were also evaluated histologically., Results: In sclerosed and non-sclerosed parts of the oesophagus EGF significantly increased the thickness of the oesophageal epithelium (P < 0.03), but failed to reduce significantly the degree of oesophageal damage associated with sclerotherapy (P = 0.11)., Conclusions: Systemic EGF treatment induces proliferation of the oesophageal mucosa, and EGF may therefore have the potential to reduce sclerotherapy-induced oesophageal damage.

Arbor Acres broiler breeder hens, 21 to 61 wk of age, were given the daily ME level recommended by the primary breeder for their age and level of production (100% AA) or were given 94 or 88% of that amount. The reduction in daily energy allotment had no effect on age at 50% or age at peak production, but there was a highly significant linear decrease in the eggs per hen from 165 +/- 2.8 in hens given 100% AA to 149 +/- 3.2 and 141 +/- 3.8 in hens given 94 and 88% AA. The percentage of nonlaying hens between 44 and 60 wk of age was substantially increased as daily energy allotment was reduced. The percentage settable eggs was significantly lower in the 100% AA group, but no differences in fertility or hatchability were seen. Chicks per hen fell from 123 +/- 2.4 to 116 +/- 2.4 to 102 +/- 2.6 as energy allotment was progressively reduced. Dietary energy allotment had no effect on egg weight, shell weight, shell characteristics, or proportion of albumen and yolk. Chick weight was unaffected but chicks' liver weight increased with increasing dam energy intake. Percentage lipid in hens' carcasses increased with increasing energy intake and percentage protein and percentage ash decreased.

The effects of daily energy intake on reproductive performance of Arbor Acres males and on growth of their offspring was studied. In Experiment 1, 21 males were placed in individual pens with 12 females. Three rations, differing in energy, were fed from 24 to 57 wk of age with seven males receiving either 300, 340, or 380 kcal ME/d. In Experiment 2, 32 individually caged males were given daily allotments of 280, 320, 360, or 360 kcal ME/d from 26 to 32 wk of age and 300, 340, 380, or 380 kcal ME/d from 32 to 38 wk. Rations of the two groups of males fed the highest energy level differed in formulation, one being the same wheat short-based basal ration as fed to the two lower energy groups, only with additional fat, and the other being a corn-soybean-based ration. Body weight and testes weight were increased with increased energy allotment in both experiments but carcass composition was unaltered. There were no significant effects of energy intake on fertility or hatchability in either experiment. Even though mean differences were not significant, fertility in two pens dropped to near zero at 38 wk in Experiment 1. Semen characteristics and plasma testosterone concentrations were unaffected by energy intake in Experiment 2. There was a significant linear increase in 6-wk BW of broilers associated with the increase in sire energy intake in each of three batches of broilers grown in Experiment 1 and in one of two batches of broilers grown in Experiment 2.

Human epidermal growth factor (EGF), a small polypeptide (6 kDa) with mitogenic properties, has been implicated in the protection of gastrointestinal mucosal integrity. The efficacy of EGF in the prevention and healing of sclerotherapy-induced esophageal lesions was investigated in 24 minipigs with surgically induced portal hypertension. In addition, the effect of EGF on intragastric acidity and pharmacokinetics was investigated as possible means to explain its protective mechanism of action. The animals underwent three weekly sessions of sclerotherapy with polidocanol 2% and were concomitantly and for an additional three weeks treated with either placebo or EGF administered paravenously in the esophagus and/or subcutaneously. The subcutaneous treatment with EGF significantly (P < 0.05) reduced esophageal stricture and scar formations associated with sclerotherapy. Gastric pH values were significantly (P < 0.01) elevated only in animals receiving subcutaneous injections of EGF. Furthermore, the subcutaneous administration of EGF was associated with unexpected prolonged plasma concentration of the peptide. These results suggest a possible clinical value of EGF as an adjunctive treatment with the sclerotherapy.

Human epidermal growth factor (EGF), a naturally occurring protein, has been implicated in the protection of gastrointestinal mucosal integrity. The efficacy of EGF in the prevention of sclerotherapy-induced esophageal lesions was investigated in 18 minipigs with surgically induced portal hypertension. The animals underwent five weekly sessions of sclerotherapy with polidocanol 2% and were concomitantly treated with either placebo or EGF administered either paravenously or subcutaneously. EGF significantly (P < 0.05) reduced esophageal ulcerations, stricture formations, and mucosal histological damage associated with sclerotherapy. The drug was well-tolerated with no overt toxicity. These results suggest a potentially important clinical value of EGF as an adjunctive treatment with the sclerotherapy.

In a prospective randomized trial the frequency of infectious complications and natural killer cell function were investigated in 197 patients undergoing elective colorectal surgery and having either no blood transfusion (n = 93), transfusion with whole blood (n = 56), or filtered blood free from leucocytes (n = 48). Postoperative infections developed in 13 patients transfused with whole blood (23%), in one patient transfused with blood free from leucocytes (2%) and in two non-transfused patients (2%) (p < 0.01). Natural killer cell function was significantly (p < 0.001) impaired up to 30 days after surgery in patients transfused with whole blood. These data provide a strong case against the use of whole blood transfusion in patients undergoing elective colorectal surgery.

Experiments were conducted to determine whether a diet with added dichloroacetate (DCA), an inhibitor of cholesterol biosynthesis, would influence plasma and egg cholesterol concentrations when fed to laying hens. In the first experiment, 62-wk-old laying hens (10 hens per treatment) were fed a control diet containing 0, 350, 700, or 1,400 ppm DCA for an 8-wk period. Egg production and size, feed intake, weight gain, and plasma and egg cholesterol were determined at biweekly intervals. In a second experiment, 36-wk-old laying hens (eight hens per treatment) received diets with 0, 3,000, or 6,000 ppm added DCA for a period of 6 wk. Production parameters and cholesterol measurements were conducted as in Experiment 1. Egg production and feed intake were significantly decreased with increasing levels of DCA in Experiment 1. In the second experiment, 6,000 ppm DCA sharply reduced feed intake, body weight, and egg production. Yolk weight and percentage yolk were significantly decreased by the higher levels of DCA used in Experiment 2. Total plasma cholesterol was not affected by dichloroacetate in either of the experiments. In contrast, egg cholesterol concentration increased by 10 and 37% in Experiments 1 and 2, respectively, in response to diets with added DCA when compared with the unsupplemented controls. Total egg cholesterol increased in response to dietary DCA in Experiment 1, but not consistently in Experiment 2 due to the decreased yolk size of the hens fed DCA. The results of these studies indicate that dietary DCA was not effective in reducing egg cholesterol concentrations.

Experiments were conducted to determine the effect of sorbose on feed consumption, egg production and size, and cholesterol metabolism of laying hens. In Experiment 1, 87-wk-old laying hens (10 per treatment) were fed diets containing 0, 10, or 20% sorbose for 4 wk. In a second experiment, 108-wk-old laying hens (eight per treatment) were fed a control diet, a diet with 10% added sorbose, or the control diet with intake restricted to the level of sorbose-treated hens for 4 wk. Feed consumption and egg production were recorded daily. Plasma and egg cholesterol levels were determined at 0, 2, and 4 wk. Plasma and egg very low density lipoprotein (VLDL) concentrations were determined after 4 wk. Egg production, feed intake, and body weight gain were significantly reduced by dietary sorbose. Egg and yolk weight and percentage yolk decreased in response to sorbose. Sorbose significantly reduced plasma cholesterol and VLDL by approximately 50%, compared with the hens fed a control diet. Egg cholesterol concentration (milligrams per gram of yolk) was significantly increased, although the reduction in yolk size resulted in similar total egg cholesterol (milligrams per egg). Restricting feed intake of laying hens significantly lowered plasma cholesterol, but not to levels comparable to that of sorbose-treated hens. The data indicate that substantial reduction of plasma cholesterol and VLDL by dietary sorbose was not accompanied by reduced egg cholesterol.

The frequency of infection in 197 patients undergoing elective colorectal surgery and having either no blood transfusion, transfusion with whole blood, or filtered blood free from leucocytes and platelets was investigated in a prospective randomized trial. Natural killer cell function was measured before operation and 3, 7 and 30 days after surgery in 60 consecutive patients. Of the patients 104 required blood transfusion; 48 received filtered blood and 56 underwent whole blood transfusion. Postoperative infections developed in 13 patients transfused with whole blood (23 per cent, 95 per cent confidence interval 13-32 per cent), in one patient transfused with blood free from leucocytes and platelets (2 per cent, 95 per cent confidence interval 0.05-11 per cent) and in two non-transfused patients (2 per cent, 95 per cent confidence interval 0.3-8 per cent) (P less than 0.01). Natural killer cell function was significantly (P less than 0.001) impaired up to 30 days after surgery in patients transfused with whole blood. These data provide a strong case against the use of whole blood transfusion in patients undergoing elective colorectal surgery.

Taurine, an amino acid synthesized from Met, primarily functions in bile acid conjugation. Four experiments were conducted to determine whether Tau supplementation of broiler cockerels and female turkey poults to 3 wk of age would influence performance and fat retention at different levels of dietary fat. In these experiments, Tau was added at 0 or .8% to a corn and soybean meal basal diet with dietary poultry fat added at 0, 5, or 10%. Taurine did not affect BW gain of broiler cockerels; however, in one experiment feed efficiency was improved (P less than .01) during the 1st wk and fat retention was improved (P less than .06) at 7 days of age. In experiments with turkey poults, dietary Tau did not affect weight gain but improved feed efficiency (P less than .01) during the 1st wk and decreased overall feed efficiency (P less than .01) in one experiment. Improvement of fat retention by Tau at 14 days was significant (P less than .02) in one experiment and approached significance (P less than .07) in the other experiment. Fat supplementation of both the broiler and turkey diets significantly (P less than .05) improved weight gain, feed efficiency, and fat retention. Supplementary Tau appears to have little effect on performance of broilers and turkeys.

Dietary alpha-ketoisocaproic acid (KIC) was studied for effects on growth, feed efficiency, tissue cholesterol (TC) content, and immune response to a Newcastle disease virus (NDV) vaccination in broilers. In two experiments, broiler chicks were fed diets supplemented with graded levels of KIC to .54% of the diet. Feed efficiency, fat deposition, BW gain, and plasma cholesterol levels were determined at 3 wk. In a third experiment, broilers were fed diets supplemented with 0, .1, .2, and .4% KIC throughout the starter (0 to 3 wk), grower (3 to 6 wk), and finisher (6 to 7 wk) periods. Abdominal fat and plasma and breast TC were measured at 7 wk. In Experiment 4, levels of KIC to .6% were fed to broilers to determine TC content and to measure the immune response to NDV vaccination. Feed efficiency, BW gain, and percentage abdominal fat were not affected by KIC in any of the broiler experiments. The addition of KIC to broiler diets resulted in a significant reduction in breast (Pectoralis major) TC. Biceps (Biceps femoralis) TC, adductor (Pubo-ishio-femoralis) TC, and plasma cholesterol content was not affected by KIC. Geometric mean titers to NDV were not improved by KIC. The data indicate that KIC has no effect on growth or abdominal fat deposition, but may have a role in TC homeostasis.

The purpose of the present study was to determine whether a polyamine deficiency could account for the reduced performance of broiler chicks fed a low-protein diet supplemented with several synthetic amino acids in comparison with those fed a more conventional CP concentration. Male broiler chicks were fed equicaloric diets calculated to contain 23, 20, or 17% CP. Each diet was supplemented with 0, .05, or .10% putrescine in a 3 x 3 factorial arrangement of treatments. Body weight gain of chicks fed the 17% CP diet was significantly (P less than .05) less than that of those fed the higher protein diets and feed conversion ratio significantly increased as the CP concentration decreased. Adding putrescine failed to significantly affect any of the parameters within each CP concentration. A deficiency of polyamines does not appear to explain the lower performance of broiler chicks fed low CP diets with added synthetic amino acids.

Experiments were conducted to determine the effect of supplemental alpha-ketoisocaproic acid (KIC) or Leu on layer performance and plasma and egg cholesterol levels. In the first experiment, 0, .09, or .27% KIC and .09 or .27% Leu were fed to 62-wk-old laying hens. In a second experiment, the same levels plus another level of .54% KIC and .54% Leu were fed to 32-wk-old hens for an 8-wk period. The basal diet or the basal diet supplemented with .27% KIC or .27% Leu were continued for 20 wk to determine the long-term effects of these supplements. In a third experiment, hens were fed 0, .1, .2, or .4% KIC for 8 wk. The addition of KIC and Leu to the hen diets did not affect percentage egg production, egg weight, shell thickness, or Haugh units. In Experiment 1, .27% KIC and .09% Leu significantly increased BW gain. Neither KIC or Leu significantly affected BW gain in Experiment 2 when measured at 8 or 28 wk. In the third experiment, diets supplemented with KIC increased significantly BW gain. In Experiment 1, .09% KIC and .09% Leu significantly reduced egg cholesterol at 4 wk. After 8 wk, .27% KIC reduced egg cholesterol significantly below the controls. No effect on plasma or egg cholesterol was observed in Experiments 2 and 3.