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Biomedical subjects

S L Jensen

Publications and source records attributed to S L Jensen.

At least 19 recordsLinked to original sources
PubMed2001

E1B-deleted adenovirus (dl1520) gene therapy for patients with primary and secondary liver tumors.

Clinical studies were performed with a recombinant mutant adenovirus with an E1B 55-kDa deletion, dl1520, to assess its toxicity and efficacy in patients with irresectable primary and secondary liver tumors. A phase I study showed that dl1520 was well tolerated when administered directly intratumorally, intraarterially, or intravenously up to a dose of 3 x 10(11) PFU. Ultrastructural examination of tissue showed the presence of adenovirus in cell cytoplasm around the nucleus and revealed two dissimilar end points of cell death after virus infection: a preapoptotic sequence and necrosis. A phase II study showed that the combination of dl1520 and 5-fluorouracil (5-FU), when infused into the hepatic artery, was well tolerated. Further improvement in the recombinant vector design will be needed in order to achieve better clinical response.

Adenoviridae↗
PubMed2000

Postoperative hepatic catabolic stress response in patients with cirrhosis and chronic hepatitis.

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.

Cholecystectomy↗
PubMed1999

Surgical gloves: current problems.

One century ago surgical gloves were introduced to practice as part of the new antiseptic technique and originally to protect the hands of the surgeon and his assistants from the harmful dermatologic effects of powerful antiseptics (e.g., carbolic acid) in use at that time. Since then, the wearing of gloves during surgery has been standard practice. Furthermore, the protection value of surgical gloves in preventing cross-infection has stood the test of time. Nevertheless, materials used in glove manufacturing have caused a succession of iatrogenic problems in surgical patients over the years. More recently, emergence of transmissible viruses, such as hepatitis B and C and human immunodeficiency virus, has led surgeons to consider their own safety with the frequent possibility of perforation of surgical gloves by sharp instruments. In this review we discuss the problems associated with surgical glove practice: glove powder-induced peritonitis and adhesions, latex rubber-associated hypersensitivity, and glove perforation.

Anti-Infective Agents, Local↗
PubMed1999

Effects of laparotomy vs pneumoperitoneum on the hepatic catabolic stress response in ambulatory and stationary settings in pigs.

BACKGROUND: We recently demonstrated that laparoscopic cholecystectomy is followed by a much smaller hepatic catabolic stress response than conventional cholecystectomy. It is not known what is responsible for this difference. METHODS: Thirty pigs were randomly allocated to the following five treatment groups: (1) laparotomy, (2) pneumoperitoneum, (3) pneumoperitoneum with insertion of four trocars, (4) laparotomy, (5) pneumoperitoneum. Groups 1-3 were operated on in an ambulatory setting, whereas groups 4 and 5 were operated on in a stationary setting. Urea synthesis, as quantified by functional hepatic nitrogen clearance, and the response of stress hormones and cytokines were assessed. RESULTS: Laparotomy increased the functional hepatic nitrogen clearance by 195% (p < 0.001); pneumoperitoneum and trocars increased it by 145% (p < 0.001); and pneumoperitoneum alone increased it by 113% (p < 0. 001). The difference between laparotomy and both pneumoperitoneum groups was significant. If the stress factor of ambulatory surgery was eliminated, the increase in functional hepatic nitrogen clearance was reduced to 87% (p < 0.01) after laparotomy and 38% (NS) for animals subject to pneumoperitoneum. There were significant differences in concentrations of stress hormones, tumor necrosis factor alpha, and interleukin 8 among groups intra- and postoperatively. CONCLUSIONS: The magnitude of the postoperative hepatic stress response after laparotomy compared to pneumoperitoneum with and without insertion of trocars seems to be caused by the greater trauma to the abdominal wall. Furthermore, an ambulatory setting seems to be an important postoperative stress factor in itself.

Ambulatory Care↗
PubMed1999

Direct comparison of projections from the central amygdaloid region and nucleus accumbens shell.

Certain neurochemical and connectional characteristics common to extended amygdala and the nucleus accumbens shell suggest that the two represent a single functional-anatomical continuum. If this is so, it follows that the outputs of the two structures should be substantially similar. To address this, projections from the caudomedial shell and central nucleus of the amygdala, a key extended amygdala structure, were demonstrated in Sprague-Dawley rats with different anterograde axonal tracers processed separately to exhibit distinguishable brown and blue-black precipitates. The caudomedial shell projection is strong in the ventral pallidum and along the medial forebrain bundle through the lateral preopticohypothalamic continuum into the ventral tegmental area, distal to which it thins abruptly. The central nucleus projects strongly to the bed nucleus of the stria terminalis and the sublenticular extended amygdala, but substantially to the lateral hypothalamus only at levels behind the rostral part of the entopeduncular nucleus. Innervation of the ventral tegmental area by the central amygdala is minimal, but the lateral one-third of the substantia nigra, pars compacta and an adjacent lateral part of the retrorubral field receive substantial central amygdala input. Central amygdaloid projections are robust in caudal brainstem sites, such as the reticular formation, parabrachial nucleus, nucleus of the solitary tract and dorsal vagal complex, all of which receive little input from the accumbens. The substantial differences in the output systems of the caudomedial shell of accumbens and central amygdala suggest that the two represent distinct functional-anatomical systems.

Amygdala↗
PubMed1999

Beneficial effects of hydrocortisone in a model of experimental acute pancreatitis.

BACKGROUND: Proinflammatory cytokines like TNF-alpha and IL-8 have been thought to play a pivotal role in the propagation of severe acute pancreatitis (AP) and the development of its systemic complications, particularly acute lung injury. OBJECTIVE: To investigate the effects of pretreatment with hydrocortisone on the production of cytokines and the occurrence of acute lung injury in rabbits with AP. METHODS: AP was induced in 17 rabbits by infusion of 5% chenodeoxycholic acid into the pancreatic duct, followed by ductal ligation. The rabbits were allocated to pretreatment with subcutaneous and intravenous hydrocortisone (25 mg/kg, respectively; n = 7) or 0.9% saline (n = 10) 30 min before induction of AP. Rabbits were observed for 12 h. Serum amylase, lipase, TNF-alpha, IL-8, glucose, calcium and leukocyte count were measured every 3 h. At the end of the experimental period, ascitic fluid was collected and tissue specimens from the pancreas, lungs and kidney were obtained. RESULTS: Hydrocortisone pretreatment improved survival from 40 to 100%. Serum TNF-alpha and IL-8 were lower in the hydrocortisone group than in the control group at 6 h (p = 0.006 and p < 0.001, respectively). Hydrocortisone abolished leukopenia (p < 0. 001), hyperamylasemia (p = 0.05), the occurrence of acute lung injury and reduced the volume of ascites. CONCLUSIONS: Our findings suggest a role for TNF-alpha and IL-8 in mediating the progress of AP from a local disease into a systemic illness. Hydrocortisone should be tested experimentally after the induction of AP and clinically as a prophylactic measure to avoid severe AP induced by endoscopic retrograde cholangiopancreaticography.

Acute Disease↗
PubMed1999

Systemic and cell-mediated immune response after laparoscopic and open cholecystectomy in patients with chronic liver disease. A randomized, prospective study.

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.

Adult↗
PubMed1999

Protein C activation during the initial phase of experimental acute pancreatitis in the rabbit.

BACKGROUND: Disturbances of coagulation and fibrinolysis are well-known systemic effects of acute necrotising pancreatitis (ANP). The purpose of this experimental study was to evaluate the initial events in the haemostatic activation during ANP in an animal model with relevance to the human situation. METHODS: ANP was introduced in 7 rabbits by infusion of chenodeoxycholic acid in the pancreatic duct. Seven rabbits served as sham-operated controls. Serial measurements of coagulation variables (prothrombin time, activated partial thromboplastin time, FVII activity, fibrinogen, tissue factor activity), anticoagulant proteins (protein C, antithrombin) and fibrinolytic factors (tissue plasminogen activator, plasminogen activator inhibitor-1) were performed for 5 h. RESULTS: ANP was confirmed by elevated serum amylase, development of ascites, and histological changes of the pancreas. A moderate activation of the coagulation system was found in both study groups. A significant decrease in protein C concentration from 1 h after the induction of ANP was found, whereas the response of antithrombin and the inhibition of the fibrinolytic system were similar in the 2 study groups. Microthrombosis of the lungs or kidneys was found in 2 rabbits with ANP. CONCLUSION: An immediate activation of protein C is a specific characteristic of the haemostatic activation in ANP in rabbits. This activation has not been described previously and the possible therapeutic implications ought to be studied.

Animals↗
PubMed1999

Graded experimental acute pancreatitis: monitoring of a renewed rabbit model focusing on the production of interleukin-8 (IL-8) and CD11b/CD18.

OBJECTIVE: To establish and monitor a rabbit model of graded severity of acute pancreatitis to test the hypothesis that interleukin-8 (IL-8) and the adhesion molecule complex CD11b/CD18 are involved in the development of systemic complications in severe acute pancreatitis. METHODS: Acute pancreatitis induction in rabbits by duct ligation with or without infusion of 5.0% or 0.5% chenodeoxycholic acid or 0.9% saline. Control animals underwent laparotomy. The animals were monitored biochemically, histologically and immunohistochemically. RESULT: Increased serum levels of IL-8, tumour necrosis factor alpha (TNF-alpha), amylase and lipase were found in the chenodeoxycholic acid groups when compared with the saline, duct-ligated or control groups. Leukopenia, hypocalcaemia, and hyperglycaemia were marked in the 5.0% chenodeoxycholic acid group as compared to the saline, duct-ligated and control groups. Histologically, the 5.0% chenodeoxycholic acid group manifested a significant degree of pancreatic necrosis and neutrophil infiltration. The lungs of these animals showed acute lung injury and a significant up-regulation of CD11b/CD18. IL-8 was produced in pancreatic acinar and ductal cells. A significantly large output of ascitic fluid was seen in the 5.0% chenodeoxycholic acid group. CONCLUSION: The rabbit models of acute pancreatitis are reliable in that enzymatic and histological evidence of acute pancreatitis with or without systemic complications developed. IL-8 is produced locally in pancreatic acinar and ductal cells and significantly increased in peripheral blood during severe but not mild pancreatitis. The expression of the adhesion molecule complex CD11b/CB18 is significantly increased in lung tissue during severe acute pancreatitis with acute lung injury. IL-8 and CD11b/CB18 are involved in the pathogenesis of severe acute pancreatitis but not of mild oedematous pancreatitis.

Acute Disease↗
PubMed1998

Tirilazad inhibits surgically induced edema and interleukin-1 production. An experimental study in rats.

The aim of this study was to evaluate the anti-inflammatory effect of tirilazad mesylate on edema and interleukin-1 (IL-1) levels in serum following standardized surgical procedures. Four groups, each containing eight rats, were randomized for treatment as follows: A) no medication, B) low-dose tirilazad, C) high-dose tirilazad, and D) corticosteroids. The animals were examined by nuclear magnetic resonance imaging (NMRI) 24 and 72 hours after surgery and the NMRI data were used in the determination of soft tissue edema. In addition, serum was obtained for analysis of IL-1 levels. Four other groups of animals were subjected to the same treatment regimen as groups A-D), respectively, and 24 hours after surgery the animals were killed, whereafter serum was obtained for analysis of IL-1 levels. The present study demonstrated that low-dose tirilazad significantly reduces soft tissue edema compared with all other treatment regimens 24 hours postoperatively. At 72 hours postoperatively significant reduction of soft tissue edema was achieved at low-dose tirilazad when compared to high-dose tirilazad and steroids. In addition, a significant suppression of the expression of IL-1 was observed at 24 and 72 hours when comparing low-dose tirilazad and the control group.

Adrenal Cortex Hormones↗
PubMed1998

Mechanical properties and collagen content differ between isolated guinea pig duodenum, jejunum, and distal ileum.

We compared the stress-strain distributions obtained from isolated segments of the guinea pig duodenum, jejunum, and distal ileum, and the relation between the elastic properties and the collagen content. The segments were immersed in Krebs-Ringer solution containing 10(-2) M MgCl2 to abolish contractile activity. Stepwise inflation of an intraluminal balloon in which the cross-sectional area (CSA) was measured provided the luminal pressure-loading stimulus. The wall thickness was measured by means of 20-MHz A-mode ultrasound. The stress-strain and the incremental elastic modulus-strain distributions were derived from the steady-state values of wall thickness, internal radius, and applied pressure. The CSA-pressure relations and the wall thickness-pressure relations were nonlinear and both differed between the segments (P < 0.01). The stress-strain distributions showed an exponential behavior that fitted well to the equation Y = a x Exp(b x X) (r2 = 0.97 +/- 0.01). The intercept with they axis (a) and the slope of the curves (b) differed between the segments (P < 0.01 and P < 0.05). The collagen contents were 3.99 +/- 0.18 microg/mg, 2.51 +/- 0.13 microg/mg, and 2.10 +/- 0.11 microg/mg in the duodenum, jejunum, and distal ileum, respectively. This difference was significant among all three locations (P > 0.05). An association was found between the collagen content and the incremental elastic modulus (stiffness) at a stress level of 70 kPa (P < 0.05).

Animals↗
PubMed1998

Sodium fusidate and the cytokine response in an experimental model of acute pancreatitis.

BACKGROUND: New therapies designed to downregulate the aberrant immune response associated with severe acute necrotizing pancreatitis (ANP) are being increasingly investigated in different experimental models of ANP. The aim of this study was to test the potential effects of sodium fusidate on the course of severe ANP in rabbits. METHODS: ANP was induced in 20 rabbits by retrograde injection of 5 per cent chenodeoxycholic acid into the pancreatic duct followed by duct ligation. The rabbits were allocated to pretreatment with intravenous physiological saline or sodium fusidate 80 mg/kg 30 min before the induction of ANP. Levels of serum amylase, lipase, tumour necrosis factor (TNF) alpha, interleukin (IL) 8, glucose and calcium, and leucocyte count were measured every 3 h for a total of 12 h. At the end of the experiment, ascitic fluid was collected and the pancreatic, lung and kidney tissues were obtained for histological examination. RESULTS: Pretreatment with sodium fusidate reduced the mortality rate from six of ten to three of ten (P < 005) and reduced the output of ascitic fluid from 5 2 to 2.0 ml/h (P < 0001). Serum levels of TNF-alpha and IL-8 were reduced significantly in the treated group from 5 min up to 9 h after induction of ANP. The leucopenia observed after 3 h in the untreated group was not significantly improved in the group treated with sodium fusidate (P = 0.055). By contrast, both treated and untreated rabbits had similar biochemical changes including levels of amylase, lipase, glucose and calcium as well as similar histological changes in the pancreas and lungs. CONCLUSION: Pretreatment with sodium fusidate resulted in a considerable reduction in mortality rate and ascitic fluid output in rabbits with bile-induced ANP, probably by lowering the TNF-alpha and IL-8 blood levels. However, pretreatment with sodium fusidate did not alter the local or systemic manifestations of ANP. Thus, cytokines other than TNF-alpha and IL-8 are likely to mediate the local and systemic symptoms of ANP.

Amylases↗
PubMed1998

A monoclonal anti-interleukin 8 antibody (WS-4) inhibits cytokine response and acute lung injury in experimental severe acute necrotising pancreatitis in rabbits.

BACKGROUND: Interleukin 8 (IL-8) has recently been proposed to have an important role in mediating the development of the systemic sequelae associated with severe acute pancreatitis. AIMS: To define the role of IL-8 in acute pancreatitis by neutralising its effects with a monoclonal anti-IL-8 antibody (WS-4), in a rabbit model of severe acute pancreatitis. METHODS: Acute pancreatitis was induced by retrograde injection of 5% chenodeoxycholic acid into the pancreatic duct and duct ligation. Twenty rabbits were divided equally into two groups: acute pancreatitis controls received physiological saline and the treated group received WS-4, 30 minutes before induction of acute pancreatitis. RESULTS: Pretreatment of animals with WS-4 resulted in significant down regulation of serum IL-8 and tumour necrosis factor alpha (TNF-alpha) from three to six hours after induction of acute pancreatitis (p = 0.011 and 0.047 for IL-8 and 0.033 and 0.022 for TNF-alpha, respectively). In addition, a significant reduction in the CD11b and CD18 positive cells and the amount of interstitial neutrophil infiltration in the lungs from WS-4 treated animals was seen. In contrast, WS-4 did not alter the amount of pancreatic necrosis and the serum concentrations of amylase, lipase, calcium, and glucose. CONCLUSION: WS-4 cannot change the amount of pancreatic necrosis induced by injection of 5% bile acid, but does reduce the acute lung injury, presumably through inhibition of circulating IL-8 and TNF-alpha, and CD11b/CD18 in lung tissue. Therefore, a role of IL-8 in the progression of acute pancreatitis and the development of its systemic complications is suggested.

Amylases↗
PubMed1998

Biliary parasites.

Parasitic diseases of the biliary tract occur frequently in tropical and subtropical areas and cause high morbidity and mortality. In general, neither the clinical presentation nor the general laboratory findings are sufficiently unique to raise the possibility of a parasitic biliary infestation in the mind of the surgeon. Once considered, however, the presence of a parasitic biliary infestation is easily confirmed. Most commonly this is accomplished by the identification of the parasite in stools or duodenal contents. Ultrasonography, CT and MRI are not only important in the diagnosis of parasitic biliary diseases but also in the follow-up and surveillance. ERCP is an excellent diagnostic tool for demonstrating the presence of parasites in the biliary tree. Furthermore, ERCP is also used in the therapy of biliary parasitic infestations and carries less morbidity and mortality than the surgical approach. Surgery is only indicated in complicated cases. Mechanisms that may be effective against parasites include: antibodies; cytotoxic T cells; T-cell-induced activated macrophages; natural killer cells, and a variety of cells that mediate antibody-dependent cell-mediated cytotoxicity and modulators of the immune system such as cytokines. Future research has to focus on the importance of these mechanisms for the immune evasion by parasites.

Animals↗
PubMed1998

Epidemiology of ankle fractures. A prospective population-based study of 212 cases in Aalborg, Denmark.

We studied the epidemiology of ankle fractures prospectively during 1 year in a population of about 200,000. The overall incidence rate was 107 fractures per 10(5) person-years. Below the age of 50, ankle fractures were commonest in men. After this age, females became predominant and the age-specific incidence rates decreased in both sexes. The main cause of fracture was falls (87%), on the ground, on stairs or from a height. 137 fractures (55%) occurred in sports, play or other leisure activities. Most patients (64%) were walking, running or jumping at the time of injury. Alcohol and slippery surfaces were each involved in nearly a third of the cases. The distribution of the fractures according to both the Lauge-Hansen and the AO Weber classification systems were within the limits of previous series. Nearly half the patients were hospitalized and the fractures were operated on with osteosynthesis. Our findings indicate that ankle fractures are mainly caused by substantial trauma sustained during physical activity. Osteoporosis seems to be of minor importance.

Adolescent↗
PubMed1998

IT 9302, a synthetic interleukin-10 agonist, diminishes acute lung injury in rabbits with acute necrotizing pancreatitis.

BACKGROUND: Proinflammatory cytokines (eg, tumor necrosis factor [TNF]-alpha, interleukin [IL]-1 and Il- 8) are believed to play an important role in the pathogenesis of acute necrotizing pancreatitis (ANP) and its systemic complications. Recently, IL-10 has emerged as a major anti-inflammatory cytokine, inhibiting the secretion and activities of inflammatory cytokines. Further, a protective effect of IL-10 has recently been shown in experimental acute pancreatitis. The purpose of this study was to test the potential role of a newly developed IL-10 agonist, IT 9302, in a model of ANP in rabbits. METHODS: ANP was induced in 18 rabbits by retrograde injection of 5% chenodeoxycholic acid in the pancreatic duct, followed by duct ligation. The rabbits were allocated to pretreatment with intravenous physiologic saline solution or IT 9302 (200 micrograms/kg) 30 minutes before the induction of ANP. RESULTS: Injection of IT 9302 resulted in a significant reduction in the blood levels of TNF-alpha and IL-8 from 3 to 6 hours. IT 9302 also reduced the amount of ascitic fluid and significantly inhibited neutrophil infiltration and margination, as well as the number of CD11b- and CD18-positive cells in the lung tissues. By contrast, the local pancreatic necrosis, as well as the biochemical changes such as serum amylase, lipase, and calcium, was sever and similar in both groups. Survival was improved significantly after treatment with IT 9302. CONCLUSIONS: As expected, IT 9302 cannot change the degree of ANP induced by 5% bile acid but does reduce mortality rates and the development of acute lung injury, probably through the inhibition of circulating levels of TNF-alpha, IL-8, and the expression of the adhesion molecule complex CD11b/CD18.

Amylases↗