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Biomedical subjects

Roland Andersson

Publications and source records attributed to Roland Andersson.

At least 19 recordsLinked to original sources
PubMed2007

Efficacy of bioactive polypeptides on bleeding and intra-abdominal adhesions.

BACKGROUND: Perioperative bleeding and postoperative adhesions are two problems encountered in abdominal surgery. Commercial products are available that decrease both bleeding and development of abdominal adhesions, but no products are effective in both situations. The combination of differently charged bioactive polypeptides, administered intraperitoneally, has previously been shown effective in decreasing postoperative adhesions. The present study is a pilot examination of the effects on perioperative bleeding and postoperative adhesions, applying the polypeptide concept. METHODS: Standardized wounds in the liver and spleen were induced in 52 NMRI mice. The amounts of bleeding and postoperative adhesions were measured after 1 and 7 days, respectively. Separate animals were examined after 8 weeks for long-term healing of the parenchymal wounds. RESULTS: Both parenchymal bleeding and the extent of adhesions significantly decreased (p = 0.001 and p = 0.029, respectively) as compared to controls. Histology after 8 weeks showed no clear signs of impaired or altered healing. CONCLUSION: Intraperitoneal administration of differently charged polypeptides significantly decreased postoperative bleeding and postoperative adhesions. Bioactive polypeptides appear promising in the promotion of peritoneal healing and merits further studies.

Abdomen↗
PubMed2006

Severe acute pancreatitis--outcome following a primarily non-surgical regime.

BACKGROUND/AIMS: Severe acute pancreatitis (SAP) is associated with a high morbidity and mortality. The aim was to evaluate treatment, risk factors and outcome in SAP in a centre with a restrictive attitude to surgery. METHODS: All cases of acute pancreatitis admitted 1994-2003 were analysed retrospectively. SAP was defined as organ failure and/or hospital stay >7 days together with one or more of: C-reactive protein >150 mg/l within 72 h after admission, necrosis on computed tomography and need for treatment in the intensive care unit. RESULTS: 185 (22%) of patients with acute pancreatitis fulfilled the criteria for SAP. 175 patients were included, mean age 61 +/- 17 years. Hospital stay was in median 13 days. Forty-six patients had some surgical intervention, in 14 cases directed at the pancreas (8%). Hospital mortality was 9% (n = 16), in 88% (n = 14) associated with multiple organ dysfunction and 50% (n = 8) of the deaths occurred within the first week after admission. Of the parameters registered on admission, age and hypotension (systolic blood pressure <100 mm Hg) were identified as risk factors for death. CONCLUSION: The present treatment regime for SAP as defined above resulted in a 9% mortality rate, with age and hypotension at admission as predictive factors for death.

Adolescent↗
PubMed2006

Immune status and inflammatory response differ locally and systemically in severe acute pancreatitis.

OBJECTIVE: Acute pancreatitis (AP) is an inflammatory disorder that develops a complex cascade of immunological events. The local and systemic immune status and inflammatory response might contribute to the understanding of underlying pathophysiological mechanisms and potential treatment. MATERIAL AND METHODS: Severe AP was induced by intraductal perfusion of 5% sodium taurodeoxycholate in rats. mRNA expression of cytokines and chemokines was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and NF-kappaB activation was assessed by electrophoretic mobility shift assay in fresh pancreatic acini and circulating monocytes 1, 3, 6 or 9 h after sham operation, induction of AP or N-acetylcysteine (NAC) pretreatment. Flow cytometry was performed on cells obtained from the peripheral blood. RESULTS: An inverse relationship in pancreatic and circulating monocytic NF-kappaB activation was detected 6 and 9 h after induction of AP. NAC further suppressed monocytic NF-kappaB activation induced by AP as seen 9 h after induction of AP. A marked constitutive increase in the expression of IL-6, CINC and MCP-1 was seen in pancreatic acini, whereas no change in mRNA expression of inflammatory mediators was observed in circulating monocytes 6 h after induction of AP. Flow cytometry further confirmed the altered function of circulating monocytes. CONCLUSIONS: The different immune status and inflammatory response in the pancreas and circulating monocytes improve the understanding of the mechanisms by which systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) develop in severe AP. A potential therapeutic approach could be to restore the functional capacity of the immune system in AP. The use of an NF-kappaB inhibitor, preferentially reaching the local inflammatory foci, could be a potential future way of intervention.

Acetylcysteine↗
PubMed2006

Treatment and outcome in pancreatic pseudocysts.

OBJECTIVE: Pancreatic pseudocyst is a common complication of both acute and chronic pancreatitis. The aim of the present study was to evaluate the efficacy and complications of different treatment regimens. MATERIAL AND METHODS: All patients > or =15 years of age admitted to Lund University Hospital from 1994 to 2003 with pancreatic pseudocysts were analysed retrospectively. Pseudocysts were defined according to the Atlanta classification. RESULTS: Forty-four patients (29 M (66%), mean age 55+/-14 years) were included in the study, and all were subjected to treatment on 88 occasions. Mean size of pseudocysts at diagnosis was 9.6+/-6.8 cm (1.5-40 cm). Recurrence after treatment was 1.0+/-1.1 times (range 0-4). No difference was found in recurrence rate or pseudocyst size when comparing conservative versus interventional treatment, but patient weight was higher (p=0.013) and acute pancreatitis was more frequent (p=0.046) in conservatively treated patients. Surgical treatment tended to be associated with a lower recurrence rate as compared with percutaneous treatments. The rate of hospital admissions was a median 3 (0-16) and median length of stay (LOS) was 12 days (0-141 days). Six patients (14%) had complications and 3 died (7%). Pseudocysts > or =8 cm did not differ significantly from smaller pseudocysts regarding the choice of conservative treatment, LOS, recurrence and gastrointestinal obstruction, but there was a trend towards more complications in the group with larger pseudocysts (5 versus 1). CONCLUSIONS: Patients with pancreatic pseudocysts require frequent hospital admissions and repeated treatments. Larger pseudocysts do not imply more recurrences. The lowest recurrence rate overall was seen after open surgery.

Adult↗
PubMed2006

Novel treatment in peritoneal adhesion prevention: protection by polypeptides.

OBJECTIVE: To evaluate a novel antiadhesive polypeptide complex containing a combination of poly-L-glutamate and poly-L-lysine in order to study its effectiveness and mechanisms in the prevention of postoperative abdominal adhesions in mice. MATERIAL AND METHODS: The length of peritoneal adhesions was measured and expressed in percentage of the wound length in a standardized peritoneal injury model and evaluated 7 days and 4 weeks after adhesion induction. The test compound was administered intraperitoneally following surgery. Peritoneal swabs, including the wound area, were stained in order to determine the peritoneal location and clearance of the polypeptides. Electron microscopy was performed to analyze the wound surface and the ultra-structural changes of the phagocytes in cell culture. Moreover, flow cytometry was used to evaluate the effect on macrophage phagocytic function. RESULTS: The poly-L-lysine and poly-L-glutamate combination significantly decreased peritoneal adhesions both at 7 days' (p < 0.001) and 4 weeks' (p < or = 0.001) follow-up. From the first day, the compound was found in the wound, after which this was gradually rebuilt, and covered with mesothelial cells. The macrophages phagocytosed the test compound particles, resulting in significant cell growth, and large phagocytic vacuoles. CONCLUSIONS: The intraperitoneal administration of poly-L-lysine and poly-L-glutamate resulted in a significant decrease in experimental postoperative peritoneal adhesions.

Animals↗
PubMed2005

Fluid resuscitation and nutritional support during severe acute pancreatitis in the past: what have we learned and how can we do better?

BACKGROUND/AIMS: Severe acute pancreatitis is associated with microcirculatory impairment, increased gut permeability and metabolic changes. The aim of the present study was to evaluate initial fluid resuscitation and nutritional support versus outcome in patients with severe acute pancreatitis. METHODS: All cases of acute pancreatitis admitted 1994-2003 were analyzed retrospectively. The inclusion criteria of severe acute pancreatitis were organ failure and/or local complications according to the Atlanta classification system. Mortality was used as outcome measure. RESULTS: Ninty-nine patients were included in the study. The hospital mortality was 17%. Hypovolemia at arrival was found in 13% (13/99) and correlated with increased hospital mortality (P=0.009). During the first three days in average 11000+/-4100 ml of fluids and 1470+/-820 calories were administered. Total parental nutrition was given to 73% (69/95) and enteral nutrition served as a complement in 29% (28/95) of the patients. Hyperglycemia was seen in 61% (55/90) of the patients and insulin was administered to 53% (29/55) at an average glucose level of 19+/-3 mmol/l. The intake of oral food was reintroduced in average 15+/-9 days after admission and was interrupted in 17% (13/75) because of pain relapse. CONCLUSION: A nutritional treatment regime in severe acute pancreatitis including a moderate and hypocaloric initial fluid resuscitation, parental nutrition as the preferred route for nutritional support and a non-strict glucose control, with an associated mortality of 17%, indicates several modes of improving outcome.

Acute Disease↗
PubMed2005

Increasing anastomosis safety and preventing abdominal adhesion formation by the use of polypeptides in the rat.

BACKGROUND AND AIMS: Postoperative adhesions can potentially be reduced using different anti-adhesive agents, though these drugs tend to compromise healing of an intestinal anastomosis. No method that significantly increases anastomosis safety is known at present. The aim of the study was to develop a concept of preventing postoperative adhesions using differently charged bioactive polypeptides, also considering healing and safety of an intestinal anastomosis. METHODS: An ileocolic anastomosis was performed under both "clean" and "septic" conditions in the rat. The treatment group received intraperitoneal poly-L-lysine and poly-L-glutamate, while controls received sodium chloride. Abdominal adhesions, anastomosis leakage and burst pressure were analysed after 1, 3, 5 and 7 days in the clean anastomosis model and after 7 days in the septic model. RESULTS: A significant decrease (p<0.01) in the amount of adhesions was seen in animals treated with polypeptides after 1, 3 and 5 days, while no difference was seen after 7 days. The anastomosis demonstrated a significantly higher burst pressure as evaluated at days 1 and 3 (p<0.05 and p<0.01, respectively) in the polypeptide-treated animals, while no difference was seen between the groups at day 5 or 7. CONCLUSION: The use of differently charged polypeptides administered intraperitoneally after surgery resulted in a significant decrease in the extent of postoperative adhesions. Furthermore, an increase in intestinal anastomosis safety, based on improved burst pressure during the first 3 days, i.e. the critical period during the healing process, was noted. No adverse effects were seen in surgery during septic conditions.

Anastomosis, Surgical↗
PubMed2005

Protein kinase C modulates the pulmonary inflammatory response in acute pancreatitis.

The present study aims at evaluating the role of protein kinase C (PKC) in the development of acute lung injury, production of inflammatory mediators and expression of adhesion molecules on leukocytes after induction of acute pancreatitis (AP). AP was induced by the intraductal infusion of 5% sodium taurodeoxycholate in the rat. The animals had the PKC inhibitor polymyxin B administered intraperitoneally 30min prior to induction of AP. Levels of protein content, protease activity, cytokines and chemokines in bronchoalveolar lavage fluid (BALF) were assessed 1 and 6h after AP induction. Adhesion molecule expression on leukocytes were measured by flowcytometry. Pretreatment with polymyxin B prevented against acute pancreatitis-induced lung injury and the otherwise occurring increases in TNF-alpha, IL-1beta, MCP-1 and IL-10, as well as against the decreases in IL-2, IFNgamma and TIMP-1, decreased protease activity and down-regulation of CD31, CD54 and CD62L on recruited neutrophils and macrophages in BALF. The results indicate that the leukocyte response in acute pancreatitis vary depending on leukocyte subpopulation. It seems that activation of the PKC signalling pathway may play an important role in pancreatitis-associated lung injury.

Animals↗
PubMed2005

Potential role of reactive oxygen species in pancreatitis-associated multiple organ dysfunction.

BACKGROUND: Severe acute pancreatitis is still associated with substantial morbidity and mortality. Experimental and clinical studies have demonstrated that reactive oxygen species (ROS) represent early occurring inflammatory mediators contributing to cell dysfunction, both locally in the pancreas and remote organs. METHOD: A systematic literature review was conducted to investigate the potential roles of intra- and intercellular, as well as interorgan signaling of ROS in the development of pancreatitis-associated multiple organ dysfunction syndrome (MODS). A text word search of the Medline, PubMed and Cochrane databases, and a manual search of the citations from these references, was performed. RESULTS: ROS directly compromise cellular damage and regulate intercellular signals in pancreatitis-associated MODS. ROS are involved in leukocyte activation, production of cytokines, endothelial barrier dysfunction, and microcirculatory barrier dysfunction in acute pancreatitis. Beside effects on intercellular signaling, ROS also affect intracellular events and activate the transcription factor nuclear factor kappa B that regulates inflammatory cytokine expression. CONCLUSION: ROS is a critical factor responsible for the development of pancreatitis-induced remote organ dysfunction via intercellular and interorgan signaling. The role of antioxidant treatment, included as a part of multimodal management, remains to be investigated.

Humans↗
PubMed2005

Intraoperative radiotherapy for patients with carcinoma of the pancreas.

BACKGROUND/AIMS: Local recurrence is one of the most common sites of failure after resection of exocrine pancreatic adenocarcinoma. Intraoperative radiotherapy (IORT) involves delivery of high doses of irradiation to the pancreas in patients with locally advanced disease, and to the surgical bed following pancreatic resection while uninvolved and dose-limiting tissues are displaced. Here we report our current experience with IORT in patients with pancreatic cancer. METHODS: IORT was given as adjuvant treatment in 18 and palliatively in 37 patients. External beam radiotherapy (EBRT) was in addition delivered to 10 patients in the resection group and 29 in the palliation group. The cancer diagnosis was verified histologically and/or cytologically in all patients. RESULTS: There was no hospital mortality. Among the resected patients the postoperative complication rate was 44% (8/18). The corresponding figure after palliative operation was 14% (5/37). None of the postoperative complications were regarded as a consequence of IORT. Symptoms and complaints were observed after EBRT in 70 and 90%, respectively, in the two groups. However, no symptom was serious in nature. After resection the median survival time was 9 months (range 3-58) and local recurrence was diagnosed in 33% (6/18). In the palliatively treated patients the median survival was 7 months (range 2-30) and pain requiring opioids was present in 89% (24/27) of the patients within 6 months. CONCLUSION: In this nonrandomized study no apparent beneficial effects were seen after IORT in patients with pancreatic cancer, neither adjuvantly nor palliatively. However, radiotherapy did not lead to any major complications.

Adenocarcinoma↗
PubMed2005

Severity of pancreatitis-associated gut barrier dysfunction is reduced following treatment with the PAF inhibitor lexipafant.

The aim of the present study was to investigate the potential effect of treatment with a platelet-activating factor (PAF) antagonist, lexipafant (BB-882), on gut endothelial and epithelial barrier dysfunction and leukocyte recruitment in rats with acute pancreatitis. Severe acute pancreatitis was induced by the intraductal administration of 5% sodium taurodeoxycholate and pancreatitis-associated gut barrier dysfunction was characterized by increased exudation of radiolabelled albumin into the interstitium and alterations in bidirectional (over both the endothelial and epithelial barrier components) permeability of the intestine at the early stage of bile salt-induced acute pancreatitis. Levels of interleukin 1beta and 6, ileal and colonic myeloperoxidase (MPO) content, clearance of radiolabelled albumin from blood to the gut lumen or gut lumen to blood, and leakage of radiolabelled albumin to the ileum or colon were measured 3 and 12h after induction of acute pancreatitis. Treatment with lexipafant 30 min and 6h after pancreatitis reduced severity of pancreatitis-associated intestinal dysfunction, associated with a diminish in systemic concentrations of IL-1 and local leukocyte recruitment. The findings imply that PAF plays a critical role in the development of pancreatitis-associated gut barrier dysfunction and that PAF antagonist in some forms may represent potential candidates for future therapeutic intervention.

Acute Disease↗
PubMed2005

Angiogenesis, endothelial cell functions, and tumor cell growth in biodegradable and nonbiodegradable devices.

Development of tissue engineering creates multiple potentials for clinical treatment and scientific research. Biodegradable collagen matrices have been found to support simultaneous autotransplantation of hepatocytes after major liver resection. Dynamic angiogenesis in biodegradable devices (BDD) and nondegradable devices (NDD) transplanted into the renal subcapsule and subcutaneous tissue was measured by the distribution of radiolabeled red blood cells and serum albumin. The circulation, microvascular integrity, and capacities of endothelial cells (adhesion, proliferation, and migration) were investigated within 2 weeks after subcutaneous transplantation of both devices. Patterns of tumor cell growth in both devices were morphologically studied. After subcutaneous transplantation, significant angiogenesis was noted at 1 week in BDD implants and from 2 weeks and on in NDD implants, with an increase in implant blood and plasma volumes. Leakage index of radiolabeled albumin in NDD implants was significantly higher than in BDD implants, while the leakage index 2 weeks after BDD implant was similar to that in subcutaneous tissues. Adhesion, proliferation and migration rates of endothelial cells isolated from both devices were higher than from subcutaneous tissues. Endothelial proliferation and migration rates in BDD implants were significantly higher at 1 week, while in NDD at 2 weeks. Tumor cells migrated and grew on the top surface of NDD with a flattened shape, while growing within the BDD forming a round mass. Endothelial capacities, angiogenetic procedure, and biological and physical characteristics of the device contribute to patterns of tumor cell growth in the device. Biodegradable collagen matrix with three-dimensional structure is suitable for simultaneous transplantation with cells without prevascularization.

Absorbable Implants↗
PubMed2005

Role of nuclear factor-kappaB, reactive oxygen species and cellular signaling in the early phase of acute pancreatitis.

OBJECTIVE: Increased knowledge of regulation of signaling proteins in acute pancreatitis (AP) could potentially contribute to the development of novel agents targeted at regulation of cellular signaling. MATERIAL AND METHODS: Severe AP was induced by administration of 5% sodium taurodeoxycholate in rats. Thirty minutes prior to induction of AP, the animals had an intraperitoneal injection of the antioxidant, N-acetylcysteine (NAC; 10 mg/kg), the NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC; 100 mg/kg), the ERK inhibitor, PD-98059 (1 mg/kg), or the tyrosine kinase inhibitor, Genistein (1 mg/kg). Plasma levels of IL-6 and IL-10 were determined by ELISA and myeloperoxidase (MPO) levels were measured in the pancreas and lungs 3 and 6 h after sham operation or induction of AP. RESULTS: AP results in significant increases in plasma levels of IL-6 at 6 h and IL-10 at 3 and 6 h. Plasma levels of IL-6 were significantly decreased after administration of NAC. NAC pretreatment also increased the ratio of IL-10/IL-6. MPO levels in the pancreas (at 3 and 6 h) and lungs (3 h) were significantly increased in animals with pancreatitis. Pretreatment with NAC, PDTC, PD98059 or Genistein significantly decreased MPO levels in the pancreas at 3 and 6 h and following the administration of PD-98059 or NAC at 6 h. Pretreatment with NAC significantly decreased MPO levels in the lungs at 3 h. CONCLUSIONS: Pretreatment with NAC could regulate the pro-and anti-inflammatory cytokine balance, probably through NF-kappaB and ROS signaling pathways. The regulation of signaling pathways during the sequestration of neutrophils in acute pancreatitis seems to vary between organs.

Acute Disease↗
PubMed2005

Prevention of postoperative peritoneal adhesions: effects of lysozyme, polylysine and polyglutamate versus hyaluronic acid.

OBJECTIVE: Intraperitoneal adhesions are an important cause of postoperative intestinal obstruction, abdominal discomfort and infertility. In the present study we hypothesized that a combination of polypeptides with different surface properties, resulting in fine disperse low-soluble complexes, could be of benefit in the prevention of abdominal adhesions. MATERIAL AND METHODS: Various polypeptides including lysozyme, polyglutamate, polylysine and combinations of all three were evaluated as compared to hyaluronic acid. A standard wound on the parietal peritoneum in mice was used and the evaluated agents were administered immediately postoperatively. The extent of peritoneal adhesions to the injured area was measured and expressed as a percentage of the wound length as evaluated after 7 days. Flow cytometry was performed to evaluate the effect on peritoneal macrophage survival and phagocytic function and the Pick test was used to determine peroxide production in order to estimate toxicity and potential impairment of macrophage function caused by the chemicals. RESULTS: Significant differences were seen among the treatment groups (p<0.001). Both polyglutamate and lysozyme, and polyglutamate together with polylysine significantly decreased adhesion formation as compared to hyaluronic acid. The polylysine-polyglutamate combination was still visible macroscopically on the peritoneal surface after 1 week, though not after 1 month. The polyglutamate-lysozyme mixture was less effective than these individual components alone. The chemicals did not show any toxic effects or altered function in macrophage cell culture. CONCLUSIONS: Lysozyme, polyglutamate and, most effectively, a polyglutamate-polylysine combination significantly decreased experimental abdominal adhesion formation. A strong mechanical connection to the wound and prolonged attendance in the surface were noted. Peritoneal phagocyte function did not seem to be influenced by the chemicals.

Adjuvants, Immunologic↗
PubMed2003

Late abdominal complaints after appendectomy--readmissions during long-term follow-up.

BACKGROUND/AIMS: The postoperative risk of small bowel obstruction is a recognized complication following appendectomy. Few studies have reconsidered the whole extent of abdominal complaints and problems following appendectomy. This study tries to evaluate the long-term outcome describing abdominal complaints requiring readmission following appendectomy. METHODS: A retrospective study of 3,230 patients undergoing open appendectomy at a single center university hospital in Sweden between 1981 and 1996. Late (>30 days) readmissions were noted and the cause for readmission and need for surgical intervention were analyzed. RESULTS: Overall, late readmissions occurred in 2.94% during a median follow-up of 10 years after appendectomy. Females predominated among those readmitted, as did patients with complicated appendicitis or a 'normal' appendix. Nonspecific abdominal pain with no sign of small bowel obstruction caused almost half of the readmissions (45%). To a large extent this group consisted of females (76%). Small bowel obstruction was seen in 1.24% and was surgically treated in 0.68% of all appendectomies. Incisional hernias were also seen (0.4% of all appendectomies). CONCLUSION: The magnitude of readmissions due to abdominal complaints is more pronounced than previously reported with as many patients with signs of small bowel obstruction managed nonoperatively as surgically, and frequent readmissions due to nonspecific abdominal pain.

Abdominal Pain↗
PubMed2003

[Guidelines for management of patients with chronic pancreatitis. Report from a consensus conference].

Chronic pancreatitis has an incidence of 3-8 new cases per 100,000 inhabitants and year. Alcohol is the most common cause. It is, however, not an independent risk factor but rather a co-factor. Smoking and genetic predisposition are increasingly regarded as causative factors. The diagnosis is today based mainly on history and findings at imaging tests. Pain treatment starts with NSAID-medication with or without paracetamol. Oral pancreatic enzyme therapy for pain should be tested early in the course. Endoscopic stent insertion into the main pancreatic duct can be used in selected cases. Operation is not recommended until other less invasive methods have been tested but should ideally be performed before addiction to opiates occurs. Oral enzyme supplementation is effective in the majority of cases with malnutrition. Most patients with chronic pancreatitis and diabetes need insulin treatment. Interdisciplinary specialist treatment teams should be established and take responsibility for diagnosis, assessment and interventional procedures (e.g. endoscopy, surgery). Due to the low incidence of the disease 3-4 such teams/centres seem appropriate in our country to allow a critical patient load.

Alcoholism↗