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Biomedical subjects

Roland Andersson

Publications and source records attributed to Roland Andersson.

At least 37 records · Page 2Linked to original sources
PubMed2003

Acute pancreatitis, expression of inducible nitric oxide synthase and defective insulin secretion.

A high level of nitric oxide (NO) produced by inducible NO synthase (iNOS) is involved in pancreatic beta-cell dysfunction and apoptosis. In the present study, we examined whether iNOS is also expressed in beta cells after induction of acute pancreatitis (AP) in the rat. Pancreatic islets taken from AP animals and incubated for 60 min in the presence of 20.0 mmol/l glucose showed a decreased insulin secretory response to glucose. The basal insulin release at 1.0 mmol/l glucose was also moderately reduced. Experiments on the dynamics of insulin secretion from perfused pancreas revealed an impairment of both first and second phase of glucose-stimulated insulin release after the induction of AP. Confocal microscopy demonstrated that most of the beta cells in pancreas of rat with AP expressed strong immunoreactivity for iNOS. This was further confirmed by biochemical and Western blot analysis that showed a marked increase in iNOS protein expression and enzyme activity concomitant with a modest reduction in the cNOS protein and activity. Although the mechanisms underlying the defective insulin secretory response of beta cells seen during the early stage of AP are complex, the present finding suggests that the expression of iNOS and a marked iNOS-derived NO production in the beta cells may play at least a contributory role in the impairment of beta-cell function.

Acute Disease↗
PubMed2003

Lactobacilli attenuate bacteremia and endotoxemia associated with severe intra-abdominal infection.

BACKGROUND: Systemic administration of antibiotics or selective decontamination is frequently used in the prophylaxis and treatment of infections originating from the gastrointestinal flora. In this study, we wanted to compare the protective effect of enteral administration of lactobacilli to gentamicin against severe intra-abdominal infection. METHODS: Male Sprague-Dawley rats underwent cecal ligation and puncture (CLP). Rats were pretreated with saline, Lactobacillus R2LC, and gentamicin. Bacterial growth and endotoxin levels in the blood, reticuloendothelial system (RES)-function, and intestinal transit were determined up to 24 hours after CLP. RESULTS: CLP-provoked bacteremia was significantly reduced by 48% and 55% in lactobacilli- and gentamicin-treated rats, respectively. Notably, CLP-induced endotoxemia was abolished at 12 hours, and reduced by 47% at 24 hours, in rats pretreated with lactobacilli. Gentamicin reduced endotoxin levels provoked by CLP by 86% at 12 hours, but had no effect at 24 hours. Lactobacilli had no effect on the clearance of Escherichia coli (E coli) from the blood, whereas intestinal transit was increased in lactobacilli-treated animals, suggesting that the beneficial effect of Lactobacillus R2LC is not related to an increase of phagocytic capacity but may rather be partly attributable to an enhanced intestinal motility. CONCLUSION: Enteral administration of Lactobacillus R2LC attenuates bacteremia and endotoxemia associated with intra-abdominal infection in rats.

Abdominal Abscess↗
PubMed2003

Retroperitoneal bronchogenic cyst as a differential diagnosis of pancreatic mucinous cystic tumor.

Cystic tumors of the pancreas where a pseudocyst has not been able to be excluded has been considered potentially proliferative and pre-malignant or malignant and thus aggressive surgical approach has been advocated. Retroperitoneal cystic tumors are rare and among these bronchogenic cysts are extremely infrequent. The present paper describes a case of bronchogenic cyst in association with the pancreas in which diagnostic work-up was not able to exclude a proliferative pancreatic cystic tumor.

Adult↗
PubMed2003

Fatal acute pancreatitis. Characteristics of patients never reaching hospital.

BACKGROUND: Mortality in acute pancreatitis is still substantial. The extent of patients dying at home due to acute pancreatitis, thus never admitted to hospital, is scarcely known. MATERIAL AND METHODS: Thirty-six patients with death caused by acute pancreatitis were identified at the Department of Forensic Medicine over a 7-year period. RESULTS: Twenty-seven patients (75%) were assumed to have alcohol as the underlying etiological factor. The duration of abdominal pain seemed short, with a median of one day. Profound pancreatitis changes were found in all patients while pulmonary changes were less frequent. CONCLUSION: Overall, up to 1/3 of patients dying from acute pancreatitis in our region seem to die at home never being admitted to hospital. The majority of instances was caused by alcohol abuse. The progression of the cause of the disease seemed rapid, implying that these patients could constitute a specific subgroup of severe acute pancreatitis.

Acute Disease↗
PubMed2003

Quality of life, morbidity, and mortality after surgical intensive care: a follow-up study of patients treated for abdominal sepsis in the surgical intensive care unit.

OBJECTIVE: To evaluate the long-term outcome of patients treated in the surgical intensive care unit (SICU) for abdominal sepsis. DESIGN: Retrospective study. SETTING: University hospital, Sweden. SUBJECTS: 210 consecutive patients treated for abdominal sepsis in the SICU at Lund University Hospital during the period January 1983 to December 1995. MAIN OUTCOME MEASURES: Background information, morbidity, and mortality. Follow-up of surviving patients with interview and completion of a quality of life (QoL) assessment. Information collected postmortem from the registers of the Swedish National Board of Health and Welfare. RESULTS: At follow-up, 45 patients of the 151 who survived the initial hospital stay had died, 41 were lost to follow up and 16 chose not to participate in the study; 49 patients completed the study. Median QoL scores were significantly impaired (p < 0.01) although subjective QoL did not change significantly. In-hospital mortality was 28% (59/210) and total mortality over the time period 50% (104/210). CONCLUSION: Most patients who survived after treatment of abdominal sepsis in the SICU regained good health and their functional status was restored. Subjective QoL remained unchanged.

Abdominal Abscess↗
PubMed2002

Effective treatment of gut barrier dysfunction using an antioxidant, a PAF inhibitor, and monoclonal antibodies against the adhesion molecule PECAM-1.

BACKGROUND: Oxygen free radicals (OFRs), platelet activating factor (PAF), cell adhesion molecules, and transmigration of polymorphonuclear leukocytes through the gut barrier are probably all essential in the development of gut barrier dysfunction following intestinal ischemia and reperfusion (I/R). Pretreatment and early treatment of I/R with the OFRs-scavenger (NAC), the PAF inhibitor lexipafant, and monoclonal antibodies against the adhesion molecule PECAM-1 (anti-PECAM-1-Mab) have been reported to be effective in the prevention or recovery of gut barrier dysfunction and result in a decrease in cytokine levels. Less is known about the effect of treatment inserted during the late stage of I/R. The objective of this study was to evaluate the potential therapeutic value of single or combination therapy with NAC, lexipafant, and anti-PECAM-1-MAb administered late during intestinal I/R in the rat. METHODS: NAC, lexipafant, and anti-PECAM-1-MAb were administrated, alone or in combination, after 3 h of reperfusion following 40 min of superior mesenteric arterial ischemia in the rat. Intestinal endothelial and epithelial barrier permeability, myeloperoxidase (MPO) activity, interleukin-1 beta (IL-1 beta), and protease inhibitor levels were evaluated after 12 h of reperfusion. RESULTS: Intestinal endothelial and epithelial permeability significantly increased in rats with I/R and saline treatment. Proteolytic activity in plasma was indicated by low levels of the three measured plasma protease inhibitors. Intestinal mucosal MPO content increased significantly. These changes were, to different degrees, reduced by late inserted treatment with NAC, lexipafant, or anti-PECAM-1-MAb. Alterations in systemic levels of IL-1 beta paralleled the changes found in gut barrier permeability and leukocyte trapping. Systemic antithrombin III levels and increased barrier permeability in remote organs were partly restored, especially by multimodal therapy. CONCLUSION: Treatment with NAC, lexipafant, and/or monoclonal antibodies against PECAM-1, inserted at a later stage of I/R, reduced the severity of I/R-associated intestinal dysfunction and decreased the systemic concentrations of IL-1 beta, local leukocyte recruitment (MPO), and partly restored plasma protease inhibitor levels.

Animals↗
PubMed2002

[Guidelines for management of patients with pancreatic cancer].

The incidence of pancreatic cancer has fallen during the last ten years in Sweden. Early signs and symptoms of the disease are still undiscovered and when diagnosis is made the disease is incurable in most patients. Transabdominal ultrasonography is the first-line imaging test followed by spiral computed tomography (CT) and magnetic resonance imaging (MRI) if required for definite diagnosis. Spiral CT is also the imaging test of choice for assessment of resectability of the tumor. Surgical removal of the tumor is the only chance of cure. Markedly improved hospital mortality after pancreaticoduodenectomy is reported and an association between hospital volume and outcome of the operation has been established. Longterm survival after attempted curative resection continues to be dismal, however. Adjuvant treatment should not be given outside clinical studies. Palliative treatment has improved thanks to progress in the field of endoscopy, interventional radiology and in management of pain and nutrition. Palliative chemotherapy should only be given selectively outside clinical studies. Radiotherapy has no proven effects on survival. Special pancreatic cancer treatment teams with catchment areas of 2-4 million inhabitants are recommended by international authorities.

Analgesia↗
PubMed2002

Management of appendiceal masses.

OBJECTIVE: To evaluate the outcome of patients treated for appendiceal abscess, and managed either conservatively or surgically, and to describe the short and long-term outcome as well as incidence of interval appendicectomy in those treated conservatively. DESIGN: Retrospective study. SETTING: University hospital, Sweden. PATIENTS: Ninety-three patients with the diagnosis of appendiceal abscess, 50 treated conservatively and 43 who were operated on, with a mean age of 46 (14-93) years. Mean (range) follow-up for patients operated on was 65 (11-135) and for those treated conservatively 66 (6-136) months. MAIN OUTCOME MEASURES: Course of acute disease, recorded complications, recurrence of appendicitis and incidence of interval appendicectomy during follow-up. RESULTS: The duration of pain before admission was 4 (0.5-82) days for those operated on and 7 (2-60) days for those treated conservatively. A palpable mass was more common in the conservatively managed group. Complications were common among patients who were operated on. No interval appendicectomies were done during the second half of the study period. 4 of the patients treated conservatively (8%) had an underlying tumour diagnosed at follow-up. CONCLUSIONS: Operative management of patients with appendiceal masses seems to be associated with a high risk of postoperative complications and the risk of a more extensive surgical procedure. If possible, a conservative approach should be advocated. Because of inaccurate radiological imaging during the acute phase and the risk of an underlying malignancy, routine follow-up is necessary. Routine interval appendicectomy cannot be recommended.

Abscess↗
PubMed2002

Percutaneous cystogastrostomy in patients with pancreatic pseudocysts.

OBJECTIVE: To evaluate the results of percutaneous cystogastrostomy for pancreatic pseudocysts secondary to acute or chronic pancreatitis. DESIGN: Retrospective study with prospective follow-up. SETTING: University hospital, Sweden. PATIENTS: 16 patients with symptomatic pseudocysts (10 men and 6 women, mean age 56 (36-78) years) treated during the period 1993-1999. INTERVENTION: Pseudocystogastrostomy was created under local anaesthesia and fluoroscopic control by percutaneous insertion of a double pigtail catheter. RESULTS: The underlying diagnosis was acute pancreatitis in 10 and chronic pancreatitis in 6 patients. 13 patients had one pseudocyst and 4 had 2 or more with a median diameter of 11 (5-20) cm. The procedure was successful in all but 2 patients, who were operated on. 2 patients experienced pain after the intervention that did not require specific treatment, otherwise no complications were noted. Median hospital stay was 2 days (range 1-60). The median follow-up was 45 (1-94) months. All but 2 patients had successful drainage during follow-up with resolution or regression of the pseudocyst and relief of symptoms (pain and abdominal discomfort). CONCLUSION: Pancreatic pseudocysts were treated by percutaneous cystogastrostomy with good results. Percutaneous cystogastrostomy is a safe, minimally invasive procedure that gives good results at long-term follow-up as well as in the short-term.

Acute Disease↗
PubMed2002

Experimental pancreatitis causes acute perturbation of energy metabolism in the intestinal wall.

INTRODUCTION: The systemic inflammatory response syndrome (SIRS) may be initiated by a number of underlying conditions such as acute pancreatitis. The association between the local inflammatory reaction, the systemic response, and potential concomitant dysfunction of remote organs is not quite clear. AIM: To evaluate whether severe acute pancreatitis in the rat affects energy metabolism in the pancreas and whether the focal inflammation also causes biochemical deterioration in remote organs such as the liver and intestine. METHODOLOGY: With the patient under general anesthesia, microdialysis probes were inserted in the pancreas, liver, and small intestine. Two groups of eight rats each were studied: the sham (control) group and the pancreatitis group. Acute pancreatitis was induced by intraductal injection of 5% sodium taurodeoxycholate, and the animals were studied for 3 hours thereafter. The microdialysis fluid was analyzed for glucose, lactate, and pyruvate. RESULTS: In the pancreatitis group we found significant increases in glucose concentration in the pancreas and lactate levels in the pancreas and intestinal wall, and the lactate/pyruvate ratio was significantly higher in the intestine than in the sham group. CONCLUSION: Induction of severe acute pancreatitis results in immediate metabolic alterations in the pancreas. In the intestinal wall a severe perturbation of energy metabolism is observed after only 1 hour. This implies a rapid onset of metabolic disturbances, not only in the local, challenged organ (pancreas) but also in remote organs.

Animals↗
PubMed2002

The effect of intestinal ischemia and reperfusion injury on ICAM-1 expression, endothelial barrier function, neutrophil tissue influx, and protease inhibitor levels in rats.

Multiple organ dysfunction syndrome (MODS) is mediated by complex mechanisms in which interactions between activated leukocytes and endothelial cells play a central role. ICAM-1 (intercellular adhesion molecule-1) mediates firm adhesion and transendothelial migration of activated leukocytes from postcapillary venules into the tissue. The present study evaluated the ICAM-1 expression in various organs after 40 min of intestinal ischemia and 1, 3, 6, 12 h of reperfusion (I/R) in the rat, using a dual monoclonal antibody technique (n = 36). Endothelial barrier permeability, using the vascular leakage of radiolabeled human serum albumin was also assessed (n = 12). Neutrophil sequestration in the lungs was quantitated by myeloperoxidase activity and plasma protease inhibitor levels were measured with electroimmunoassay. Significant regional differences were found in ICAM-1 expression between organs, both constitutively and after I/R-injury. The highest constitutive levels were observed in the liver and lungs, followed by the kidneys. The constitutive ICAM-1 expression in the intestines and in the heart was about 1/20 compared with that found in the liver and lungs. The brain and muscle had levels of about 1/150 of that in the liver and lungs. After intestinal I/R, significant increases (17-45%) were found in the lungs, intestines, brain, heart, and muscle. Albumin leakage index (ALI) in all examined organs and myeloperoxidase activity in the lungs increased after I/R-injury. Serum levels of albumin and most protease inhibitors decreased significantly after I/R challenge. Intestinal I/R results in an increase of systemic ICAM-1 expression with marked organ variability. The upregulation of ICAM-1 could represent a crucial step in the adherence- and migration process of activated leukocytes and potentially in the development of tissue injury.

Albumins↗
PubMed2002

NF-kappaB activation and inhibition: a review.

Among transcriptional regulatory proteins described, NF-kappaB seems particularly important in modulating the expression of immunoregulatory genes relevant in critical illness, inflammatory diseases, apoptosis, and cancer. In particular, NF-kappaB plays a central role in regulating the transcription of cytokines, adhesion molecules, and other mediators. The biochemical basis by which diverse stimuli converge to activate or intervene this family of transcription factors is still largely unknown. The NF-kappaB transcription factor family represents an important group of regulators of a broad range of genes involved in cellular responses to inflammatory and other kinds of signals. Knockout mouse studies have also revealed a key role for this family in broad physiological processes, including immune function and metabolism. Overall, specificity seems to exist in the role of each transcriptional complex in gene transcription and physiological function. Each NF-kappaB complex displays distinct affinities for the different DNA-binding sites present in the promoters of NF-kappaB-regulated genes, and this may contribute to some of the specificity exhibited. The identification of specific components of the NF-kappaB signal transduction pathway provides an opportunity to define mechanisms at the biochemical level by which specific members of the NF-kappaB family are activated. Furthermore, this may identify specific targets for selective inhibition or promotion of NF-kappaB functions. Further studies will be required to elucidate mechanisms regulating specificity and selectivity of NF-kappaB function, as well as its role in different diseases, prior to potential clinical application.

Animals↗
PubMed2002

Mast cells contribute to early pancreatitis-induced systemic endothelial barrier dysfunction.

BACKGROUND: Activated mast cells can produce and release a number of inflammatory mediators involved in the pathophysiological process of acute conditions. The aim of the study was to evaluate the effect of mast cell stimulation on the early development of multiple organ dysfunction (MODS) in acute pancreatitis (AP). METHODS: AP was induced by the intraductal infusion of 5% sodium taurodeoxycholate in the rat. Tissue endothelial barrier dysfunction (TEBD) was measured by plasma exudation of radiolabeled albumin. Activation of mast cells was estimated by measuring the release of histamine. Mast cell stimulation was achieved with compound 48/80 (C48/80) administered intravenously (i.v.) or intraperitoneally (i.p.) in different doses either as pretreatment (30 min prior to induction of AP) or treatment immediately after induction of AP. RESULTS: Administration of C48/80 both i.p. and i.v. demonstrated the same effects. A single pretreatment dose of C48/80 (0.5 mg/kg) significantly reduced AP-induced TEBD in the pancreas and gut. Administration of C48/80 immediately after sham operation or induction of AP resulted in a significant increase in pancreatic and intestinal TEBD (p < 0.05 vs. AP+saline). Plasma levels of histamine increased with increasing doses of C48/80. CONCLUSION: The results imply that mast cell activation could be involved in the initiation of AP and the early phase of AP-induced MODS. Mechanisms seem to be complex and are still to be elucidated.

Acute Disease↗
PubMedDate not supplied

Alterations of adhesion molecule expression and inflammatory mediators in acute lung injury induced by septic and non-septic challenges.

The lung is frequently the first failing organ during the sequential development of multiple organ dysfunction under both septic or non-septic conditions. The present study compared polymorphisms of tumor necrosis factor (TNFalpha), monocyte chemoattractant protein-1 (MCP-1), and adhesion molecule (AM) expression on circulating, recruited, and migrating leukocytes in the development of lung injury after induction of acute pancreatitis (AP) or abdominal sepsis by cecal ligation and puncture (CLP). Pulmonary alveolar barrier and endothelial barrier permeability dysfunction were measured. The expression of AMs (CD11b, CD11b/c, CD31, CD54 and CD62L) on leukocytes isolated from blood, lung tissue, and bronchoalveolar space were measured by flowcytometry. Plasma exudation to the interstitial tissue and the bronchoalveolar space significantly increased 1 and 3 hours after induction of pancreatitis and to the bronchoalveolar space from 6 hours after sepsis. Bronchoalveolar levels of MCP-1 significantly increased earlier than plasma exudation to the alveoli in both pancreatitis and sepsis. Alterations in expression of adhesion molecules on bronchoalveolar lavage (BAL) leukocytes can represent a marker reflecting leukocyte activation in the lung tissue, since both BAL and lung tissue leukocytes showed similar patterns of changes. Expression of adhesion molecules on circulating leukocytes increased 1 hour after induction of pancreatitis. Activating phenotypes of circulating, lung tissue and bronchoalveolar leukocytes may thus be responsible for the-development and severity of secondary lung injury.

Acute Disease↗
PubMedDate not supplied

Influence of mast cells on the expression of adhesion molecules on circulating and migrating leukocytes in acute pancreatitis-associated lung injury.

Pancreatitis-associated lung injury is an early-occurring and severe complication, still associated with substantial mortality. A number of inflammatory cells and their products are involved in the initiation and progress of the condition. In the present study, acute pancreatitis (AP) was induced by the intraductal infusion of 5% sodium taurodeoxycholate in the rat. Pulmonary endothelial barrier dysfunction was measured by plasma exudation of radiolabeled albumin. Expression of PECAM-1, ICAM-1, and L: -selectin on neutrophils (CD11b(+)) and monocytes/macrophages (CD11b/c(+)), obtained from circulation and lung tissue, was measured 1 and 6 hours after AP induction (n = 10 rats/time point/group). Plasma levels of histamine and serotonin were determined. The role of mast cells was evaluated by pretreatment with the mast cell stabilizer cromolyn. Intraperitoneal administration of cromolyn downregulated pancreatitis-induced systemic increase of histamine at 1 hour (513 +/- 82 vs. 309 +/- 50, p < 0.05). Cromolyn prevented a decreased expression of PECAM-1 on circulatory neutrophils and monocytes/macrophages and against an increased expression of ICAM-1 and PECAM-1 on pulmonary neutrophils and monocytes/macrophages 6 hours after AP induction (about 40% vs. 10%, p < 0.01). The mast cell stabilizer also prevented pancreatitis-induced pulmonary endothelial barrier dysfunction at 6 hours. Thus, our data indicate that mast cells may play a critical role in the activation of leukocytes during the initiation of pancreatitis-associated lung injury by altering phenotypes of adhesion molecules.

Acute Disease↗
PubMedDate not supplied

Proteomics and leukocytes: an approach to understanding potential molecular mechanisms of inflammatory responses.

Leukocytes play an important role in the progression of disease and leukocyte-derived proteins are associated with the pathogenesis of the disease. Leukocyte activation causes production of inflammatory mediators, over-expression of cell surface adhesion molecules, and an increase in migration and infiltration, phagocytosis, and degranulation, as well as receptor phosphorylation and signal transduction. An increasing number of studies on the application of leukocyte proteomics have appeared in mapping protein profiles of inflammatory cells, contributing to the understanding of potential mechanisms involved in leukocyte function. Together with improvements in proteomic technology in leukocyte research, leukocyte proteomic analysis becomes more simple, rapid, flexible, sensitive, and specific. This enables proteomic investigation of activated or non-activated leukocytes to be highly focused on defined suborgans or specific signaling pathways. Research in leukocyte proteomics is progressing from fingerprinting to functioning, human cell lines to primary leukocytes, non-activated cells to inflammatory mediator-stimulated cells, in vitro culture to in vivo challenge, and animal models to human disease. A number of newly identified proteins from leukocyte proteomics may offer new mechanism-orientated targets for drug discovery and development.

Dendritic Cells↗